Criteria for IRB Approval: 45 CFR 46.111 (DHHS), 21 CFR 56.111 (FDA), and 38 CFR 16.111 (VA)
The federal regulations governing human subjects research specify the conditions under which a research study can be approved and re-approved by an IRB. DHHS, FDA, and VA regulations outline identical criteria that an IRB must determine are met in order to approve non-exempt research involving human subjects. The staff reviews and primary reviewer checklists are designed to reflect these requirements and to help ensure all of the federally prescribed criteria for IRB approval of a research protocol are met with each review.
NOTE: IF THE IRB DOES NOT FIND THAT A PROTOCOL MEETS ALL THE CRITERIA NOTED BELOW AT THE TIME OF INITIAL OR CONTINUING REVIEW, IRBS ARE EXPECTED TO DEFER OR DISAPPROVE THE PROTOCOL.
Criteria That Must be Met for IRB Approval
The DHHS, FDA, and VA regulations all describe that the following must be in place in order for an IRB to approve a research protocol involving human subjects:
- The IRB must find that risks to subjects are minimized.
- Risks are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result from the research.
- Selection of subjects is equitable.
- Informed consent will be sought from each prospective subject or the subject's legally authorized representative and appropriately documented in accordance with, and to the extent required by the DHHS, FDA, or VA regulations.
- When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
- When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
- When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.
Guidance for IRBs: Identification of Risks and Benefits
- In the process of determining what constitutes a risk, only those risks that may result from the research, as distinguished from those associated with therapies subjects would undergo even if not participating in research, should be considered.
- In behavioral, social, and some biomedical research, the methods for gathering information may pose the added risk of invasion of privacy and possible violations of confidentiality.
- Another potential risk to subjects is the possible long-range effect of applying the knowledge gained through research.
- The benefits of research fall into two major categories: benefits to subjects and benefits to society.
- Research may involve subjects who are undergoing treatment, diagnosis, or examination for an illness or abnormal condition. This kind of research often involves evaluation of a procedure that may benefit the subjects by ameliorating their conditions or providing a better understanding of their disorders.
- Other research is designed principally to increase our understanding and store of knowledge about human physiology and behavior. Research that has no immediate therapeutic intent may, nonetheless, benefit society as a whole. These benefits take the form of increased knowledge, improved safety, technological advances, and better health.
- Direct payments or other forms of remuneration offered to potential subjects as an incentive or reward for participation should not be considered a "benefit" to be gained from research.
Guidance for IRBs: Risk/Benefit Analysis
- Risk/benefit assessments will depend on whether the research: (1) involves the use of interventions that have the intent and reasonable probability of providing benefit for the individual subjects; or (2) only involves procedures performed for research purposes.
- In research involving an intervention expected to provide direct benefit to the subjects, a certain amount of risk is justifiable.
- In studies designed to evaluate therapies for life-threatening illness, risk of serious adverse effects may be acceptable. However, in any trial of a new or not-yet-validated treatment, the ratio of benefits to risks should be similar to those presented by any available alternative therapy.
- In research where no direct benefits to the subject are anticipated, the IRB must evaluate whether the risks presented by procedures performed solely to obtain generalizable knowledge are ethically acceptable. There should be a limit to the risks society (through the government and research institutions) asks individuals to accept for the benefit of others, but IRBs should not be overprotective.
- If only minimal risks are involved IRBs do not need to protect competent adult subjects from participating in research considered unlikely to yield any benefit.
- In reviewing any protocol, IRBs should:
- obtain complete information regarding experimental design and the scientific rationale (including the results of previous animal and human studies) underlying the proposed research, and the statistical basis for the structure of the investigation
- analyze the beneficial and harmful effects anticipated in the research, as well as the effects of any treatments that might be administered in ordinary practice, and those associated with receiving no treatment at all
- determine whether the investigators are competent in the area being studied, and whether they serve dual roles that might complicate their interactions with subjects
- assess whether the research design will yield useful data
- assess whether adequate safeguards are incorporated into the research design, such as frequency of monitoring, the presence of trained personnel who can respond to emergencies, or exclusion of individuals or classes of subjects whose vulnerability to a drug or procedure may increase with the risks to them
- ensure provisions are made for monitoring the data as they accumulate to assure the safety of patients, to assure that no group or subgroup in a trial is compromised by a less effective treatment, or ensure the trial does not continue after reliable results have been obtained