Guideline on Federal and UAB Requirements for the Protection of Human Research Participants: Ethical and Legal Framework for Human Research Protections at UAB
Proper attention to the protection of human research participants1 is of vital importance to UAB’s clinical research activities. Ethical considerations form the foundation for protecting participants, and today regulatory law embodies the ethical review procedures for the vast majority of medical and behavioral research in the United States. This summary is intended to provide investigators with a synoptic overview of the ethical and legal approach to human research participant protections at UAB. Since federal regulation dominates the research landscape in this area, much of the material has general applicability.
A significant advance in the application of ethics to human research was the development of specific codes of ethics for research. The first and most widely known of these codes is the Nuremberg Code, which was published in 1947 following the trial of Nazi physicians for human research-related atrocities. Subsequently, other ethical codes for human research protections were developed such as the Declaration of Helsinki, the Belmont Report, and the International Ethical Guidelines for Biomedical Research Involving Human Subjects.
For its human research activities, UAB applies the ethical principles published in the Belmont Report, "Ethical Principles and Guidelines for the Protection of Human Subjects of Research," authored by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report provides the ethical basis for the United States’ federal regulations pertaining to the protection of human research participants. The Declaration of Helsinki published by the World Health Organization has been adopted by many nations outside of the United States, and investigators doing international research at UAB should inquire about what ethical principles apply in the country where their studies are taking place.
The Belmont Report contains three basic principles:
Respect for humans refers to a competent individual’s prerogative to make a knowing and voluntary decision to participate in human research without the threat of undue influence or coercion. Frequently termed the principle of autonomy, this principle demands that participants give informed consent. Beneficence refers to the concept of overall benefit to the participant. Whether or not beneficence is attained is determined by weighing both the potential absolute benefits and harms to the participants. Potential harm to research participants should always be minimized and, secondarily, benefits maximized. Generally, individual rights may not be sacrificed to achieve an overall societal good. The third principle, justice, refers to fairness. In the context of human research participation, this is frequently determined by whether the benefits to be gained from the research justify the burdens placed on the individuals studied. A recent example involving the principle of justice centered about the unfairness created by testing of AIDS drugs in African countries in which there was no possibility for the population to benefit from treatment with the drugs after experimentation was completed.
Federal agencies have addressed human protections for research under their jurisdiction by promulgating regulations using federal administrative law. A federal regulation has the force and effect of law and when valid may preempt state laws. The major federal regulations pertaining to human research protections are the Federal Policy for the Protection of Human Subjects (The Common Rule, 45 CFR 46 Subpart A) adopted by 17 federal agencies, the Supplemental Protections for Pregnant Women and Fetuses, Prisoners, and Children promulgated by the Department of Health and Human Services (DHHS), the Food and Drug Administration (FDA) regulations on human subject protections, and the recently promulgated Health Insurance Portability and Accountability Act (HIPAA) privacy regulations administered by the Office for Civil Rights in DHHS. In most instances, more than one set of these regulations apply to a research protocol; when this is the case, each set of regulations must be satisfied independently of each other.
To receive research funding from the DHHS, each institution must hold an assurance with DHHS to abide by its regulations for human research protections. The same requirement for agency assurance holds for research sponsored by other federal agencies that have adopted the Common Rule. UAB holds a federalwide assurance which is valid for federally funded research sponsored by any of the 17 agencies requiring an assurance. UAB’s federalwide assurance is the institution’s written, binding commitment filed with the federal government that promises to comply with applicable regulations governing human subjects research and states the procedures which must be utilized to achieve compliance. Through its federalwide assurance, UAB applies the DHHS regulations for human research protections (45 CFR 46 Subparts A, B, C, D) to all applicable human research activities regardless of the source of funding for a study. In addition, UAB must satisfy the applicable FDA regulations on human subject protections and HIPAA regulations.
Finally, state law controls the legal age for consent. In Alabama, the age of majority is 19 years; therefore, an 18-year-old does not hold adult status and cannot be legally bound without parental consent. This differs from most states where the age of majority is 18 years. Confusion sometimes arises because in Alabama several exceptions exist that allow individuals under 19 to consent to medical treatment. For instance, Alabama statute §22-8-4 states that any minor who is 14 years of age or older may give effective consent to any legally authorized medical, dental, health, or mental health services for himself or herself, and the consent of no other person shall be necessary. This statute has not been applied to medical research activities per se even though it may apply to standard medical procedures within the context of a research protocol. Because of Alabama’s age of majority, UAB review of research protocols including 18-year-olds as eligible enrollees utilize DHHS and FDA rules for additional protections in children.
Public and federal emphasis on human research protections will likely intensify in the future, as evidenced by increased federal oversight, current enthusiasm for accreditation for human research protection programs, and the public notoriety generated by the recent death of a teenage participant in a gene therapy trial. Having a good understanding of the overall framework for human subjects protection will assist stakeholders in the clinical research enterprise to meet their responsibilities in this area.
1 The terms participant and subject are use interchangeably in this guideline.
Approved on March 1, 2010, by:
Richard B. Marchase
Vice President for Research and Economic Development