Minimal Risk is a regulatory term defined in the common rule (45 CFR 46.102(i)) and by the FDA (21 CFR 50.3(k)). It is not based on opinion alone, but on a defined standard.
Note: For research involving prisoners, a separate definition is applied (45 CFR 46.303(d)).
Minimal Risk Definition
“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.
This definition is used by the IRB to make a yes/no decision about whether or not the identified risks in a study meet this test. To make a decision they have their background and expertise, the internet, your application, any references or background you include and the possibility of asking for an external consultant. The burden is on the applicant/researcher to demonstrate an understanding of the risks and the methods used to assure the risks appropriately minimized.
Breaking Down the Definition
A. The daily life of whom?
The regualtory definition does not specify whose daily life is to be considered. An arguement can be made that the risks of daily life vary significantly from one population to another. The risk of a new combination of drugs might be no increase over the risks of the standard drug combinations taken by that group. If daily risk is establshed based on the individual, many risky studies could be considered minimal risk.
Most IRBs set the standard using an ‘Everyman’ approach, similar to the legal term, as the Everyman of a conceptual Average American. As every IRB has members from vastly different backgrounds and experiences, each IRB has the potential to reach differing conclusions.
B. Doing what in daily life or during procedures?
Again, these must be procedures that our conceptualized average American Everyman might encounter on a daily basis or might encounter during a routine physical or psychological examination.
The definition distinguishes risks from routine tests or examinations. Having a skin growth (mole, skin cancer, warts) removed, reviewing a Beck depression scale or completing a test in a magazine or on Facebook are quite usual and pose a routine risk. What do lots of people do or experience on a daily basis? The question for an IRB reviewer is whether an equivalence can be found that is ordinarily encountered in daily life.
C. What is the harm?
The nature of the harm should be named or specified instead of simply referring to “a risk”. It is a risk of something specific happening. The harm can be physical, mental, emotional, social, legal, financial or community. The definition includes discomfort. Discomfort is quite subjective but must again be evaluated by the IRB members.
D. Probability of harm
Risk is a statement of probability that a given harm might occur. Presumably a high probability (99%) of a mild harm (rated 1 out of 10) is a risk, but cosidered minimal. A more challenging question is whether or not a low probability (0.005%) of a high magnitude harm (10 out of 10) is still considered minimal, The harm is significant, but the risk of that harm is vanishingly small. Such a determination is made on a case-by-case basis by the IRB, and the reasoning is documented. It shoudl be noted that the consent form rules only require that the risk be listed if it is “reasonably foreseeable”.
E. What is the severity of the Harm?
As part of the determination process, the IRB will consider questions like the following: For the person who has become the 1 in the 1/1000 ratio, what is the predicted severity or magnitude of the harm? What is the most likely result and what is the worst-case result? What can be done to minimize the severity? In biomedical studies death is often the worst-case scenario. With survey studies, the magnitude might be a question that could lead one to have a psychotic event or to be identified as a part of a stigmatized group.