Explanation of Federal Regulations for Human Subjects Research, Part 2
Author(s):
Elysa Koppelman Ph.D.
Largely in response to morally suspicious and in many cases morally atrocious behavior by some researchers, the welfare and rights of human research participants came to the forefront of public debate. Infamous cases like the Nazi experiments and the Tuskegee Syphilis Study revealed the need to take measures to protect human subjects from physical, social, and psychological harm. Public debate revealed the need to bring fundamental ethical principles to bear on research in a formal way through federal and institutional regulations and to assure compliance with these regulations through the establishment of committees like the IRB.
Documents like the Belmont Report, the Nuremburg Code and Helsinki Declaration discuss ethical principles that are relevant to engaging in research with human subjects. There are three main ethical principles discussed in the Belmont Report, each of which gives rise to several of the federal regulations (45CFR46). These regulations, in turn, require researchers to think about how they design their research projects. Each of these principles, the regulations to which they give rise, and the implications they have for research design will be discussed below.
Justice
The Principle of Justice
The authors of the Belmont Report claim that "considerations of justice, as they relate to research with human subjects, focus on questions like `who ought to receive the benefits of research and bear its burdens?'" According to this definition, an injustice occurs when someone or a group of people is denied access to some benefit to which they are entitled or when someone or a group of people is unduly burdened. In other words, it is important that equals be treated equally.
The Federal Regulations (45CFR46)
The principle of justice is reflected in two federal regulations, both of which focus on the concern that people not be unduly burdened. Researchers and the IRB will work together to assure that:
- The selection of research subjects must be equitable. This assessment should take into account the purposes of the research and the setting in which it will be conducted. Researchers and the IRB should also be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, or economically or educationally disadvantaged persons.
- When some of all of the subjects are likely to be vulnerable to coercion or undue influence, researchers and the IRB should assure that additional safeguards have been included in the study to protect the rights and welfare of these subjects.
NIH Regulations
If your research is being funded by the NIH, there are two more regulations with which you should be concerned. This regulation focuses on the concern that people not be unduly excluded from the possible benefits of research.
- It is the policy of NIH that women and minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification establishes to the satisfaction of the relevant institute/center director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research . . . The inclusion of women and members of minority groups and their subpopulations must be addressed in developing a research design appropriate to the scientific objectives of the study.
- It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
Research Design
When you are designing the recruitment mechanism of your research, be sure to keep this principle and these regulations in mind. You should not recruit subjects because "they are easily available or manipulated or in a compromised position" but rather for "reasons directly related to the problem being studied" (Belmont Report). If your research is funded by the NIH, you must examine not only your methods and criteria for including subjects, but also for the exclusion of subjects.
Back to Top
Beneficence
The Principle of Beneficence
The "principle of beneficence" expresses the idea that one should benefit (and refrain from harming) others. Whereas considerations of justice or fairness address the question of who benefits and who bears burdens, considerations of "beneficence" concern producing the greatest good while minimizing harm. When considering benefits, one can consider both the benefits to particular participants and the benefits gained from the knowledge generated by research. When considering harm (risk) one considers the probability and magnitude of harm.
The Federal Regulations (45CFR46)
The principle of beneficence essentially requires making risk-benefit assessments. This is reflected in the following federal requirements:
- Risks to subjects must be minimized to the greatest extent possible by
- using procedures that are consistent with sound research design and which do not unnecessarily expose subjects to risk and
- whenever appropriate, by using procedures already being performed on subjects for diagnostic or treatment purposes.
- Risks to subjects must be reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
- In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from research (as distinguished from risks and benefits of therapy subjects would receive even if not participating in the research).
- The IRB will not consider possible long range effects of applying knowledge gained in research (such as possible effects on public policy) as among the research risks that fall within the purview of its responsibility.
Research Design
When you are designing your research protocol, you should strive to have the best risk-benefit ratio that is possible without compromising your scientific goals. If you can design your research in a way that reduces risk or increases benefits to participants without compromising your scientific objectives (by, for example, not having a placebo arm or using blood already taken for therapeutic purposes), you should. Bear in mind that potential participants will also use risk-benefit assessments to aid in their decision to participate. It is in your best interest on a number of fronts to design your research projects with this assessment in mind.
Back to Top
Respect for Persons
The Principle of Respect for Persons
Respect for persons has two aspects:
- Treat autonomous agents (those capable of forming goals and plans and of acting on them) as such.
- Protect those with diminished autonomy.
Aspect (a) tells us that people should be allowed to make informed and voluntary choices about participating in research. Aspect (b) tells us that people who are unable to make such choices need to be protected.
Regulations
The first aspect of the principle of respect for persons is embodied in the requirement to obtain informed consent from potential participants. The Office for Protection from Research Risks (OPRR) explains that informed consent "is the fundamental mechanism to ensure respect for persons through provision of thoughtful consent for a voluntary act." (The second aspect is embodied in the special regulations for some vulnerable populations like children, fetuses, and prisoners to be discussed separately.) There are two regulations that focus on informed consent.
- Informed consent must be sought from each prospective subject or the subject's legally authorized representative.
- Informed consent must be properly documented.
The process of obtaining informed consent must conform to the requirements of 45CFR46.116 and the documentation of it must conform to the requirements of 45CFR46.117. OPRR explains these requirements and gives helpful suggestions in its Tips on Informed Consent.
Research Design
It is important that you understand that informed consent is a process, not a form, and it must be present throughout your research design. Information is presented to potential participants so that they can voluntarily decide whether or not to participate in a particular research project. OPRR explains that "the procedures used in obtaining informed consent should be designed to educate the subject population in terms they can understand."
The informed consent document is part of the informed consent process. You may either have a written form that contains all of the required elements or a short form written consent which states that all of the elements of informed consent have been presented orally to the subject or subject's legally authorized representative. (When the second option is chosen, you must have a witness to the oral presentation.) OPRR has a checklist of the basic (and additional) elements of the informed consent document.
When you think about informed consent, think about how you can help assure that potential subjects are making informed, voluntary choices about whether to participate. You should provide them with all of the necessary information needed to make a good choice. If you leave out important information, their choice will not be an informed one. You should also be careful of the language you use, as some language can seem coercive and this would undermine the goal of enabling potential subjects to make voluntary choices.
Waiving Informed Consent
If your research protocol qualifies for expedited review, it may also qualify for a waiver of a signed informed consent form. The IRB may waive the requirement for the investigator to obtained a signed informed consent form for some or all of subjects, if it finds that:
- the research involves no more than minimal risk to the subjects;
- the waiver or alteration will not adversely affect the rights and welfare of the subjects;
- the research could not be practicably carried out without the waiver or alteration; and
- whenever appropriate, the subjects will be provided with additional pertinent information after participation.
If you believe your protocol meets these four characteristics, you may apply to the IRB for an informed consent waiver. Your IRB will make the final determination as to whether your protocol qualifies for the waiver. Check with your IRB for information about how to make such an application.