Research by its very nature involves exploring areas about which little is known and usually involves risks. In the course of human subjects research, subjects may be exposed to risks and may be harmed as a result of their participation. Among an investigator’s most important ethical obligations are to minimize the probability of harm to subjects, maximize the benefits derived from the research, and never knowingly cause subjects to suffer or be permanently injured. In addition to minimizing the probability of harm, all protocols, in order to be considered ethical and to be approved by an Institutional Review Board (IRB), must ensure that the risks (the probability and magnitude of harms) to which subjects are exposed are reasonable in relation to the benefits expected to accrue to the individual or to society in general, through the generation of new knowledge. An acceptable risk-benefit relationship must exist.
In order to determine if a protocol’s risks are reasonable in relation to the anticipated benefits, investigators must identify the risks and potential benefits of the research, objectively estimate their magnitude and the likelihood of their occurrence, and perform a risk-benefit analysis. This risk-benefit analysis often involves categorizing a study’s procedures or interventions into therapeutic and nontherapeutic components and analyzing these separately. When completed, the risk-benefit analysis presents an accurate and complete accounting of a protocol’s risks and benefits. A description of these risks and benefits is incorporated into the protocol, submitted for review by the IRB and, when approved, presented to prospective subjects during the process of informed consent.
Because vulnerable subjects may have difficulty providing informed consent (understanding and protecting their own interests) or because their circumstances may subject them to intimidation and exploitation, they are given special protections. One such protection is to place limits on the level of risk to which these subjects may be exposed as research subjects.