370. Assessing Reasonableness of Risks in Relation to Benefits

Updated July 1, 2021

A benefit is generally defined as a desired outcome or an advantage. Research benefits include anticipated or expected outcomes resulting from a research project, or what researchers hope to discover following implementation of the research plan.

Research benefits fall into two categories:

benefits to participants and
benefits to society.

Beneficence is identified as one of three ethical principles that should underlie the conduct of human research in the Belmont Report. The principle of beneficence involves doing no harm and maximizing possible benefits and minimizing possible harms. Beneficence requires that research participants be protected against risk of harm while consideration is given to the loss of possibly substantial benefits that might be gained from human research. Brutal or inhumane treatment of human participants is never morally justified.

Federal regulations for the protection of human participants at 45CFR46.111 item (2) specify that for the IRB to approve a research project, risks to participants must be reasonable in relation to anticipated benefit to participants (if any) and the importance of the knowledge that may reasonably be expected to result.

Investigators and the IRB have an obligation to ensure research is designed to yield useful data. While good research design may not reduce or eradicate risks to participants, poor or faulty research design diminishes the likelihood the research will achieve the desired benefits.

Given these considerations, investigators and the IRB must determine when:

it is justifiable to seek certain benefits despite the risks involved, and
the benefits should be foregone because of the risks.

Benefits to Participants Versus Benefits to Society

Participants may benefit when research involving evaluation of a treatment, diagnosis, or examination for an illness or abnormal condition is designed to ameliorate their conditions. However, even when a direct diagnostic or therapeutic benefit to participants is anticipated, investigators:

must fully inform participants about both the risks and voluntary nature of participation; and
must NOT inflate or overly emphasize possible benefits.

Society may benefit from research that is designed to increase understanding and scientific knowledge about human physiology, cognition, behavior, or educational practices. Such research may:

not be related to treatment or diagnosis of illnesses or conditions the participants have; or
may be related to participants' conditions but does not carry an immediate therapeutic intent.

Benefits to society include increased knowledge; improved safety; technological advances; or enhanced understanding of a behavior, disorder, or condition.

IRBs should not be overprotective of participants or dismissive of the importance of the knowledge that may result from a research project. Interests other than those of the individual participant may be sufficient to justify the risks involved in a research project if each participant's rights are adequately protected. If only minimal risks are involved, IRBs do not need to protect competent adult participants from participating in research that may yield concomitantly minor benefits.

Assessment of Risks in Relation to Research Benefits

To determine if risks to participants are reasonable in relation to possible research benefits, investigators and the IRB must:

consider only those benefits that may result from the research; and
NOT consider possible long-range effects of applying the knowledge gained in a single research study as benefits of that study.

Analysis of risks and benefits should be as methodical and non-arbitrary insofar as possible, requiring:

thorough accumulation and assessment of information about all aspects of the research; and
systematic consideration of alternatives to the proposed procedures (when equally suitable and viable alternatives exist).

The IRB application requires investigators to:

state the study purpose;
provide background information in support of the research;
describe study procedures (including alternative procedures);
identify expected risks (if any) including magnitude and probability of the risks;
explain how risks are minimized; and
describe expected benefits to participants and to science or society.

The IRB reviews the information provided by the investigator to:

evaluate the soundness of the research design with consideration for minimizing risk and limiting unnecessary exposure of participants to risk;
determine if benefits are appropriately identified and consistent with the study purpose and procedures; and
assess the reasonableness of risks in relation to the anticipated research benefits.

The IRB's evaluation of research risks and benefits requires examination of the validity of assumptions and presumptions about the research. The review will also analyze the scientific or scholarly validity of the proposed research. The IRB will carefully consider the study design and overall scientific quality of each study, particularly those studies that are investigator-initiated and/or unfunded. In evaluating the scientific design, the primary reviewer (exempt and expedited studies) or the primary reviewer and convened IRB (full board studies), will consider the following:

clarity of the research question
appropriateness and efficiency of design
rigor and feasibility of methods
qualifications and expertise of the research team
scholarship and pertinence of background material and rationale
adequacy of sample size and relevance of controls and
the validity of the statistical analysis plan.

When necessary, the IRB may ask consultants with additional expertise to review the research study.

For example, the IRB may use known facts and information from available studies to evaluate the reasonableness of the investigator's:

identification of expected harms and benefits, and
assessment of the magnitude and probability of expected harms and benefits.

In assessing existing knowledge about the research, the IRB must exercise professional judgment in remaining cognizant that:

information drawn from animal research may be highly suggestive of the risks and benefits to be expected for humans, but is not conclusive; and
the absence of data concerning risks does not necessarily mean that no risks exist.

The justifiability of research should reflect at least the following considerations:

Is it in fact necessary to use participants to achieve the research objectives?
Are risks are reduced to include only those necessary to achieve the research objective?
Are lower risk alternative procedures used whenever possible?
Is the involvement of vulnerable populations appropriate and necessary given the research objective?
Are there characteristics of the sample population that might alter perceptions of risks and benefits? (For example, the terminally ill may view risks of physical discomfort differently that would healthy participants.)
Does the research involve interventions that have the intent and reasonable probability of providing benefit for the individual participant or is the research designed primarily to contribute to scientific knowledge?

For greater than minimal risk research, the IRB must determine the acceptable nature, magnitude, and probability of risk for research involving an intervention expected to provide direct benefit to the participant. The IRB may determine that for studies designed to evaluate therapies for life-threatening illness, risk of serious adverse effects may be acceptable. Conversely, the IRB may determine that research involving significant risk of serious impairment must provide some benefit to the individual participant. Such determinations require:

evaluation of risks and benefits of available alternative therapies (for research involving experimental treatment/interventions);
evaluation of the nature and degree of risk, the condition of the population involved, and the nature and level of the anticipated benefits; and
thorough disclosure and discussion of the salient risks and benefits in the informed consent process.