Determining the Level of Risk

What does minimal risk mean in regulation?

In addition to identifying risks and evaluating whether risks are minimized, and evaluating whether risks are reasonable in relation to anticipated benefits, if any, IRB committee members are asked to determine the level of risk.

Reviewers should make one of the following determinations about the level of risk:

• The research involves no more than minimal risk to subjects.
• The research involves more than minimal risk to subjects.
• (This section does not address additional required determinations about level of risk when reviewing of research involving pregnant women, children, or prisoners; see help in those sections of the application)

Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (45 CFR 46.102(h)(i)). This is the definition of minimal risk in "Subpart A" of the regulations.

• Under Subpart A, the regulatory definition of minimal risk distinguishes research that is eligible for expedited procedures from research that requires review by the convened IRB (note other considerations apply to research involving pregnant women, children, and prisoners)
• Minimal risk defines a threshold for other regulatory provisions, such as alterations or waivers of the process of informed consent, and documentation of consent.
• OHRP has not issued formal guidance on the definition of minimal risk, though the issue has been studied by the Secretary's Advisory Committee on Human Research Protections.

Apply the regulatory definition to research: First identify risks and then compare risks in the research against the "daily life" standard

IRB committee members, or reviewers using the expedited procedure, should identify risks in the research, considering the nature of the study procedures, other study characteristics, the participant characteristics, and the steps proposed by the researcher to minimize risk. When identifying risks, reviewers should consider characteristics of subjects to be enrolled in the research (newly diagnosed patients? experienced patients? well-educated patients?), including an evaluation of subject susceptibility, vulnerability, resilience, and experience in relation to the anticipated harms and discomforts of research involvement. Then reviewers should compare risks with the threshold of risks encountered in the routine experience of "the average person" in daily life. This is the "daily life" standard.

Reviewers should focus on the risks posed by the treatments or procedures involved in the research. For example, the DOH IRB might review a request to access the Florida Cancer Registry Data System as part of a large study of efficacy of surgical reconstruction secondary to breast cancer. Normally in a case like this, DOH's involvement is limited to just the provision of the data from the Cancer Registry. So when reviewing this request, reviewers should focus on just those parts of the research in which the Department is engaged--in this example, on just the use of the Cancer Registry Data, and not on the surgery.

An ethically meaningful notion of "harms and discomforts ordinarily encountered" should reflect "background risks" that are familiar and part of the routine experience of life for "the average person" in the "general population." The definition of minimal risk should not shift relative to specific patient populations or circumstances. For example, if the background risks encountered in the "daily lives" of adult patients with cancer or HIV were used to set the minimal standard, then the threshold might be set too high, because the background risks of such patients may include burdensome medical interventions like radiation therapy or significant drug side effects. Just because a patient population may be accustomed to a relatively high background risks as part of treatment should not cause reviewers to alter the threshold for minimal risk. For example, patients requiring dialysis or mechanical ventilation or other intensive procedure should not have a different "minimal risk" threshold just because their "daily lives" expose them to higher background risks. Instead, minimal risk should be applied in manner that recognizes that risks are procedure-specific and population-dependent, but that the notion of "acceptably-low" risk is fixed.