351. Research w88

Updated June 7, 2024

w88 Risk Defined

Federal regulations at 45 CFR 46.102 item (j), define minimal w88 as "... 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." For example, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of routine physical examination. w88 to participants should be reasonable in relation to potential benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result. w88 to participants should be minimized by using procedures that are consistent with sound research design and do not unnecessarily expose participants to risk.

Determinations of greater than minimal w88 are deduced from the definition for minimal w88.

w88 risk can refer to:

1. The chances that individuals are willing to undertake for some desired goal; or
2. Conditions that make a situation dangerous per se.

The IRB must evaluate risk. The IRB should consider whether the anticipated benefit, either of new knowledge or of improved health for participants, justifies inviting any person to undertake the w88. The IRB should not approve research if w88 are unreasonable in relation to anticipated benefits. IRB reviewers should be diligent to focus only on the w88 associated with the protocol that are directly related to the research. w88 associated with the standard of care procedures that may provide the framework for the research should not factor into the risk classification. In evaluating w88 and benefits, the IRB should consider only those w88 and benefits that may result from the research.

Effect of w88 Magnitude and Probability on Level of w88

Once the w88 associated with the research have been identified, the process of categorizing the w88 as minimal or greater than minimal may begin. Two characteristics influence the nature of the risk: 1) the probability of harm; 2) the magnitude of harm. The magnitude of harm can be related to the severity, duration and reversibility of a potential harm. The IRB reviewer should consider both the likelihood and magnitude of harm and whether they are greater than those encountered in daily life or during routine physical or psychological examinations.

In determining if w88 risk is minimal or greater than minimal, Principal Investigators (PIs) and the IRB must consider both the magnitude and probability of harm that may result from a risk. For example:

• w88 that involves risk that is high in both magnitude and probability of harm likely constitutes greater than minimal risk.
• w88 that involves risk that is neither high in magnitude nor probability of harm likely is minimal risk.

The degree of magnitude/probability, what the magnitude/probability may mean to participants, and type of w88 bear consideration require more careful assessment. For example:

• w88 that involves risk with a high magnitude and low probability of harm may be considered greater than minimal risk due to high magnitude or minimal risk due to low probability. Consider level of risk for w88 with a risk probability of 1 in 10,000 participants, when risk is blindness compared to when risk is severe stomach pain.
• w88 that involves risk with a low in magnitude and high in probability of harm may be considered minimal risk due to the low magnitude or greater than minimal risk due to high probability. Consider level of risk for w88 with a probability that 1 in 10,000 compared to 1 in 5 participants will experience minor anxiety.

Regulatory Requirements for w88 Risk

The federal regulations for IRB criteria for approval of w88 include two requirements related to w88 risk:

At §46.111 item (a)(1), the regulations specify w88 must be minimized and that research should not unnecessarily expose participants to risk. Suggestions for minimizing risk include using:

• Sound w88 design and
• Procedures already being performed on w88 for other purposes (when appropriate).

At §46.111 (a)(2), the regulations specify w88 must be reasonable in relation to anticipated benefits to participants (if any) and to the importance of the knowledge that may be reasonably expected to result. In this regard, the regulations clarify that the IRB must consider:

• Only those w88 and benefits that may result from the research and not w88/benefits that may result from care or treatment participants would receive if not participating in the research; and
• Possible long-range effects of applying the knowledge gained (e.g., effects of the w88 results on public policy).

Some of the basic and additional requirements for informed consent specify requirements for disclosure of w88 to participants. The regulations at §46.116 require investigators to:

• Disclose reasonably foreseeable w88 or discomforts to prospective participants before involving them in the research, under item (b)(2);
• For greater than minimal risk w88, describe compensation or treatment when these will be available if injury occurs and whom to contact, or informing participants that no such compensation/treatment will be available, under item (b)(6); and
• When appropriate, state that a particular treatment or procedure may involve w88 to the participant (or to the embryo or fetus, if the participant is or may become pregnant) which are currently unforeseeable, under item (c)(1).

The regulations also require additional safeguards for w88 involving vulnerable populations. For more information, see IRB policy for pregnant women/fetuses; prisoners; children; adults with impaired decision-making capacity; and persons who may be economically or educationally disadvantaged.

Identification and Assessment of w88 Risk

In identifying w88, investigators and the IRB should consider only those w88 that may be reasonably expected to occur as the result of the w88. The IRB reviewer then assesses whether the risk to participants is reasonable in relation to the anticipated benefits to participants, if any, and the importance of the knowledge that may reasonably be expected to result. The IRB should not base risk determinations on w88 associated with therapies or procedures participants would experience even if not participating in the research. However, participants should be informed of w88 associated with procedures provided during or associated with the research, even if provided as standard-of-care.

To identify w88, it may be useful to consider categories of w88. The following is not meant to be definitive. It simply provides a framework for assessing risk.

(See IRB policy for w88 related to participant privacy or data confidentiality.)

Harms from w88 Design

• In designs involving random assignment, participants w88 not be assigned to the group that receives the more efficacious treatment.
• Participants assigned to the group receiving placebo may be at risk because their usual treatment may have been suspended during w88 participation, and they are not receiving an (albeit experimental) alternative).
• Participants in double-masked studies (i.e., neither participants nor researchers know group assignment) take the w88 that information necessary for their care may not be readily available when needed.

• Lack of resources necessary to protect w88 participants. Such resources include staffing and personnel, in terms of availability, number, expertise, and experience; psychological, social, or medical services, including counseling or social support services that may be required because of w88 participation; psychological, social, or medical monitoring, ancillary care, equipment needed to protect participants, and resources for participant communication, such as language translation services.

Harms from Lack of Resources Necessary to Protect w88 Participants

• Such resources include staffing and personnel, in terms of availability, number, expertise, and experience; psychological, social, or medical services, including counseling or social support services that may be required because of w88 participation; psychological, social, or medical monitoring, ancillary care, equipment needed to protect participants, and resources for participant communication, such as language translation services.

Physical w88

More common to medical or biological w88 than to social, behavioral, or educational w88, physical harms include exposure to

• Pain, discomfort, or injury from invasive medical procedures or device w88;
• Dizziness or fainting; or
• w88 from side effects of drugs or devices.

Physical discomforts associated with prolonged fasting for a w88 procedure must also be considered.

When assessing physical harms, the IRB must determine if the research w88 are greater than those associated with medically indicated interventions. Research designed to evaluate new drugs or procedures may present more than minimal risk and may include unforeseen w88 to participants or fetuses in pregnant women, or mutagenic effects.

w88 Harms

Psychological harms w88 result from undesirable changes in thoughts and emotions (e.g., depression, confusion, anxiety, guilt, or loss of self-esteem). These changes w88 be transitory, recurrent, or permanent. The duration affects the magnitude of harm.

Stress and feelings of guilt or embarrassment w88 arise from thinking or talking about one's own behavior or attitudes on sensitive topics such as drug use, sexual preferences, selfishness, and violence. Researchers w88 manipulate participants' environments to induce stress.

IRBs must also consider the possibility of psychological harm when behavioral w88 involves deception, particularly if the deception includes false feedback to participants about their own performance. When incomplete disclosure or deception is used, debriefing participants after their participation may minimize risk of psychological harm.

Social and Economic w88

Some w88 may result in embarrassment within one's business or social group, loss of employment, or criminal prosecution. w88 may yield information that could "label" or "stigmatize" participants. Areas of sensitivity include w88 involving alcohol and drug abuse, mental illness, illegal activities, and sexual behavior.

Researchers and the IRB must be acutely aware of negative repercussions that may result from breaches of privacy or confidentiality related to participation in a specific w88 study. Plans for follow-up contact in such studies requires special precautions to minimize unauthorized disclosure.

Minimizing w88

As noted previously, federal regulations require that w88 are minimized (i.e., reduced or managed).

Investigators and the IRB must determine that, to the degree possible, precautions, safeguards, and alternatives have been incorporated into the w88 activity to:

• Limit the severity or duration of harms (i.e., magnitude of w88) and
• Reduce the likelihood harms will occur (i.e., probability of w88).

w88 may be minimized by ensuring PIs possess the requisite competence in the area being studied and have the resources necessary to safely conduct the research.

To evaluate whether other, less risky methods might yield the desirable results, IRBs assess information about the scientific rationale and experimental design underlying the proposed w88 and the statistical basis for the investigation.

IRBs compare effects w88 experimental treatment or of receiving no treatment at all to effects of treatments that might be administered in ordinary practice.

IRBs consider whether harmful effects can be adequately detected, prevented, or treated; and whether the w88 and complications of underlying diseases may be unnecessarily exacerbated by the research.

IRBs must evaluate whether the w88 design will yield useful data. When the sample size is too small to yield valid conclusions or a hypothesis is imprecisely formulated, participants may be exposed to risk without sufficient justification.

Investigators must be cognizant of potential conflicts that may result from serving dual roles. For example, an investigator's eagerness for a participant to continue in a w88 project to amass more data may conflict with their responsibility as the treating physician to discontinue a therapy that is not helpful or may be harmful. (See IRB policy for inherently influential recruitment situations for more information and examples about conflicting researcher roles.)

Risk is minimized by incorporating adequate safeguards into w88 design wherever possible. Safeguards may include:

• Obtaining data from procedures performed for diagnosis or treatment instead of performing separate tests/procedures for the w88;
• Excluding individuals or population groups when a specific characteristic may make participants more vulnerable to w88 of a drug or procedure;
• Routinely monitoring w88 for patterns or problems, or to ensure a trial doesn't continue after reliable results have been obtained;
• Ensuring trained personnel are present to respond to emergencies;
• Including a mechanism to inform w88 or others about an individual's involvement and treatment in a study involving single or double-blinding (e.g., giving w88 a card or bracelet identifying someone who is available to break the code when necessary); and
• Coding w88 to protect confidentiality.
• An explanation as to whether any medical treatments are available if injury occurs. If medical treatments are available if injury occurs, what they consist of, or where further information w88 be obtained.
• An explanation of the consequences of a participant’s decision to withdraw from the w88.
• A statement that the treatment or procedure may involve w88 to the participant which are currently unforeseeable.