Risks and Benefits of Research

The IRB is responsible for evaluating the potential risks and weighing the probability of the risk occurring and the magnitude of harm that may result. It must then judge whether the anticipated benefit, either of new knowledge or of improved health for the research subjects, justifies inviting any person to undertake the risks. The IRB cannot approve research in which the risks are judged unreasonable in relation to the anticipated benefits.

What is the Requirement?

45 CFR 46.111 (a) (1) Risks to subjects are minimized:

(i) By using procedures that are consistent with sound research design and that do not unnecessarily expose subjects to risk, and

(ii) Whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (e.g., the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

How do I Comply With the Requirement?

Initial Review Application

You will be asked to select all procedures that will be conducted for research purposes as directed by the study protocol:

Analysis of information or specimens collected for reasons other than this project (medical records, student records, research records collected for another study, analysis of left-over specimens, etc.)
Non-invasive procedures to collect information or specimens (interviews, questionnaires, observation, vitals, oral swabs, urine collection, etc.)
Collection of blood by finger stick, heel stick, ear stick, or venipuncture
Use of xrays or microwaves
With the exception of collection of blood by finger stick, heel stick, ear stick, or venipuncture, collection of information or specimens when the collection requires penetration of tissue (tissue biopsy, implantation of a device, etc.)
Use of medical drugs or devices in a manner already approved by the FDA
Use of medical drugs or devices in a manner not approved by the FDA

Your selection will assist in routing the application for the appropriate level of review.

Research Protocol

Describe the known risks related to participation in research. Describe any actions taken to minimize risk. Clearly state which procedures are being done specifically for research purposes and which are done as standard of care or normal practice.

Describe any anticipated benefits the research subjects may receive from participation in the research. For minimal risk research, there is no requirement of direct benefit to research subjects; it is acceptable to state that there is no anticipated benefit to subjects. When research is greater than minimal risk, the anticipated benefits must justify the known risks. Please note that compensation for participation in research may not be listed as a benefit.

Consent Documents

Describe the known risks and anticipated benefits in laypersons terms. List all risks and benefits that are described in the research protocol.

Ethical Considerations

When making this determination in research with adult populations, the IRB weighs the risks to participants against the anticipated benefits (either direct or indirect) of the research. When vulnerable subjects take part, the regulations place limits on the extent of risk permitted. Children may only participate in greater than minimal risk research when there is a prospect for direct benefit. The IRB will:

Identify and compare the risks associated with the research from the risks of therapies or alternatives to participation in research.
Determine that the risks will be minimized.
Identify the anticipated benefits to be derived from the research.
Determine that the risks are reasonable in relation to be benefits to subjects, if any, and the importance of the knowledge to be gained.
Verify research participants will be provided with an accurate and fair description (during the consent process) of the risks and/or the anticipated benefits.

Risk Guidance

In human subject research, research is categorized into in two categories:

Minimal risk; or
Greater than minimal risk

Research is considered minimal risk when the risks of the research are not greater than those experienced in regular daily life. Researchers are responsible for identifying any possible risks of the research and minimizing risks to subjects whenever possible. Some common types of risks are:

Economic risks: Payment by subjects for procedures not otherwise required, loss of wages or other income and any other financial costs, such as damage to a subject’s employability, as a consequence of participation in the research.
Loss of Confidentiality: In all research involving human subjects, confidentiality of identifiable information is presumed and must be maintained unless the investigator obtains the express permission of the subject to do otherwise. Subjects have the right to be protected against injury or illegal invasions of their privacy and to preservation of their personal dignity. The more sensitive the research material, the greater the care that must be exercised in obtaining, handling, and storing data. In order to minimize the risk for loss of confidentiality, investigators should only collect personal information that is absolutely essential to the research activity. If personal data must be collected, it should be coded as early in the activity as possible and securely stored so that only the investigator and authorized staff may access it. Identities of individual subjects must never be released without the express consent of the subject. In addition, if an investigator wishes to use data for a purpose other than the one for which it was originally collected and the data are still identifiable (e.g. a code list for the data still exists), the investigator may need to obtain consent from the subjects for the new use of the data.
Legal risks: Legal risks exist when the research methods are such that the subject or others will be liable for a violation of the law, either by revealing that the subject or others have or will engage in conduct for which the subject or others may be criminally or civilly liable, or by requiring activities for which the subject or others may be criminally or civilly liable.
Physical risks: Physical risks include physical discomfort, pain, injury, illness or disease brought about by the methods and procedures of the research. A physical risk may result from the involvement of physical stimuli such as noise, electric shock, heat, cold, electric magnetic or gravitational fields, etc. Engaging a subject in a social situation which could involve violence may also create a physical risk.
Psychological risks: The potential for negative affective states such as anxiety, depression, guilt, shock and loss of self-esteem and altered behavior. Sensory deprivation, sleep deprivation, use of hypnosis, deception or mental stresses are examples of psychological risks.
Social risks: The potential for alterations in relationships with others that are to the disadvantage of the subject, including embarrassment, loss of respect of others, labeling a subject in a way that will have negative consequences, or in some way diminishing those opportunities and powers a person has by virtue of relationships with others.

Strategies for Minimizing Risks

Eliminating Risks

Risks are eliminated by limiting research procedures or data collection to those that are necessary for the research. Some examples:

Recording data without identifiers.
Collecting the minimum data necessary for the research.
Performing only procedures that are necessary to achieve the study objectives.
Collecting the fewest specimens with the least volume necessary.

When risks cannot be eliminated, there are often opportunities to decrease the risk to research subjects. Some examples:

Use of existing records or specimens.
Use of a blood-drawing IV instead of separate venipunctures for a PK study.
Obtaining a certificate of Confidentiality to minimize the likely of forced disclosure of sensitive materials.
Coding data and samples to conceal identifiers.
Using REDCap to secure data that includes PHI.
Limiting access to research data.

Combining research procedures with clinical care

If procedures can be timed to take place at the same time as a clinically indicated procedure or if clinical test results can be used instead of repeating the measurements, the risks are often greatly reduced. Some examples:

Timing research blood draws, X-rays or other procedures to occur at the same time as clinical procedures.
Limiting research MRI, PET, CT or other scans, to those having a clinically indicated study, particularly when sedation or general anesthesia is required.

Benefits Guidance

Nancy King has defined three types of benefit that may occur in the context of clinical research (J Law Med Ethics. 2000 Winter;28(4):332-43)

Direct Benefit: A benefit arising from receiving the intervention being studied.

Indirect Benefits

Collateral Benefit is a benefit arising from being a subject, even if one does not receive the experimental intervention (for example, a free physical exam and testing, free medical care and other extras, or the personal gratification of altruism).
Aspirational Benefit is a benefit to society and or future patients, which arises from the results of the study.

Research with a direct benefit

Any study that involves an intervention could have an anticipated direct benefit. In these studies, participants may receive some intervention (medical, behavioral, or other), that they would not otherwise receive. The purpose of the research is typically to test the effectiveness of the intervention. When describing the anticipated benefits of research in the consent document, it is important that researchers make subjects aware that the benefits of the intervention are not known, and that the research is being conducted to evaluate the effectiveness of the intervention. Whenever possible, the researcher should provide any known information about the probability and magnitude of the anticipated benefit.

Research with an indirect benefit

When research does not involve an intervention there is little opportunity for direct benefit. When the risks of the research are no greater than those encountered in the everyday life, there is no requirement for direct benefit. When the research risks are greater than minimal risk, then the researcher must provide justification that explains how the anticipated benefits of the research justify the risks to the subjects.

Definitions

Benefit is a valued or desired outcome; an advantage.
Minimal Risk means 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.