Explanations of general guidelines and federal regulations for human subjects research.
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.
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 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:
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.
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.
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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 principle of beneficence essentially requires making risk-benefit assessments. This is reflected in the following federal requirements:
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.
Respect for persons has two aspects:
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.
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.
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.
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.
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:
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.