IRB FAQs – Review Mechanisms

When is research considered exempt?

Under federal regulations, certain categories of activity are considered research but may be declared exempt from review by the IRB. However, at ECU, as at most institutions, this does require completing a brief application via the electronic submission system and submitting it to the UMCIRB for consideration. The primary investigator (PI) cannot, because of potential conflicts of interest, make this determination. It must be made by the UMCIRB.

What are the categories of research that are exempt from review?

The following are the exempt categories as listed in §45 CFR 46.104(d):

Category No. 1: Research conducted in established or commonly accepted educational settings that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction. This includes,

Most research on regular and special education instructional strategies, and
Research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Category No. 2: Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:

The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, e.g. coding numbers;
Any disclosure of the human subjects’ response outside the research would not reasonably place the individual at risk of criminal or civil liability or be damaging to the person’s financial standing, employability, educational advancement or reputation; or
The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review.

Category No. 3: Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:

The information obtains is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
Any disclosure of the human subjects’ response outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or
The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subject, and an IRB conducts a limited IRB review.

If the research involves deceiving the subjects regarding the nature or purpose of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware or misled regarding the nature or purposes of the research.

Benign behavioral interventions are defined in the revised common rule as brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. Provided all such criteria are met, examples of such benign behavioral interventions would include having subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.

Category No. 4: Secondary research for which consent is not required. Secondary research uses of identifiable private information or identifiable bio-specimens, if at least one of the following criteria is met:

The identifiable private information or identifiable bio-specimens are publicly available;
Information, which may include information about bio-specimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;
The research involves only information collection and analysis involving investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, sub-parts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45CFR164.512(b); or
The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non-research activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.

Category No. 5: Research and demonstration projects that are conducted or supported by a Federal Department or agency or otherwise subject to the approval of department or agency heads, and that are designed to study, evaluate, improve, or otherwise examine public health benefit or service programs, including:

Procedures for obtaining benefits or services under those programs;
Possible changes in or alternatives to those programs or procedures; or
Possible changes in methods or levels of payment for benefits or services under those programs.

Such projects include, but are not limited to, internal studies by Federal employees, and studies under contracts or consulting arrangement, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities such as sections 1115 and 1115A of the Social Security Act, as amended.

Each Federal department or agency conducting or supporting research and demonstration projects must establish, on a publicly accessible Federal website or in such other manner as the department of agency head may determine, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision. The research or demonstration project must be published on this list prior to commencing the research involving human subjects.

Category No. 6: Taste and food quality evaluation and consumer acceptance studies if:

Wholesome foods without additives are consumed, or
Food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration (FDA) or approved by the Environmental Protection Agency (EPA) or the Food Safety and Inspection Service of the U. S. Department of Agriculture (USDA).

**The exempt categories above are applicable to Sub-part D, which provides for additional protections of children involved as participants in research except for categories No. 2 and No. 3. Exempt category No. 2(a) and (b) may apply to research in children involving educational tests or the observation of public behavior when the investigator(s) do not participate in the activities being observed. Exempt category No. 2(c) does not apply to research involving children.

***The exempt categories above are not applicable to human research activities involving prisoners, except for research aimed at involving a broader subject population that only incidentally includes prisoners.

What is limited IRB review?

Limited IRB review ensures there are adequate provisions for protecting privacy and maintaining confidentiality and provides privacy safeguards to reduce the chances that the disclosure of identifiable private information will occur and lead to harm. Limited IRB review is a condition for exemption of research activities certified exempt under the following categories:

Exempt Category No. 2: Identifiable and sensitive educational tests, survey procedures, interview procedures, or observation of public behavior; and
Exempt Category No. 3: Identifiable and sensitive benign behavioral interventions

What is an expedited review?

The criterion to be eligible for expedited review is that the study cannot be greater than minimal risk. IRBs must evaluate research studies in terms of the risk the research poses to human participants. The IRB should also review the informed consent process according to the level of risk posed. Expedited review is review of proposed research by the IRB chair or their designee rather than by the full committee. Research involving no greater than minimal risk, minor changes in previously approved research (amendments), and research for which limited IRB review is a condition of exemption may all receive expedited review. If the risk to the subjects is greater than minimal, full IRB review is warranted.

What are the categories of research that may be reviewed via an expedited review procedure?

Category No. 1: Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

Research on drugs for which an investigational new drug application (21 CRF Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.) or
Research on medical devices for which (i) an investigational device exemption application (21 CRF Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

Category No. 2: Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

From healthy, nonpregnant adults who weight at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8-week period and collection may not occur more frequently than two times per week;
From other adults and children, considering age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8-week period and collection may not occur more frequently than two times per week.

Category No. 3: Prospective collection of biological specimens for research purposes by non-invasive means. Examples:

Hair and nail clippings in a non-disfiguring manner;
Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;
Permanent teeth if routine patient care indicates a need for extraction;
Excreta and external secretions (including sweat);
Un-cannulated saliva collected either in an unstimulated fashion or stimulated by chewing gum base or wax or by applying a dilute citric solution to the tongue;
Placenta removed at delivery;
Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;
Supra- and sub-gingival dental plaque and calculus provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques;
Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings;
Sputum collected after saline mist nebulization.

Category No. 4: Collection of data through non-invasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.) Examples:

Physical sensors that are applied to either the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject’s privacy;
Weighing or testing sensory acuity;
Magnetic resonance imaging;
Electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography;
Moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

Category No. 5: Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. This listing refers only to research that is not exempt.)

Category No. 6: Collection of data from voice, video, digital, or image recordings made for research purposes.

Category No. 7: Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. This listing refers only to research that is not exempt.)

What is the definition of minimal risk?

Minimal risk, defined in 45 CFR 46.102, is defined such 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. Please note that there are special circumstances which are taken into consideration with research involving prisoners as research subjects.

For research involving prisoners, additional regulations must be applied. These additional regulations at §45 CFR 46, Subpart C, define “minimal risk” as follows:

“Minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons (§45 CFR 46.303(d))”

The wording of the Subpart C definition differs in several ways from the definition of “minimal risk” in 45 CFR Part 46, subpart A which applies to human research as a general population. The differences are:

Subpart C definition refers to “physical or psychological harm” rather than “harm or discomfort” as in subpart A.
Subpart C definition compares the probability and magnitude of harm in the research to the probability and magnitude of those harms normally encountered in daily life, or in “routine medical, dental or psychological examinations,” rather than in daily life or “routine physical or psychological examinations or tests” as in subpart A.
Prisoner regulations define “healthy persons” as the comparison group against which the risks of the research should be measured, rather than leaving the comparison group unspecified, as in subpart A. OHRP interprets the term “healthy persons” in this definition as referring to healthy persons who are not prisoners.

What is the definition of full board review?

When full board review is necessary, the research proposal is presented and discussed at a meeting at which a quorum of IRB members is present. For the research to be approved, it must receive the approval of a majority of those voting members present.

What happens if the study was not approved by the full committee or if it requires changes?

The investigator will receive electronic notification documenting the committee’s findings typically within 48 hours.

What are the criteria for IRB Approval?

In order to approve research, the IRB must ensure that the following requirements are satisfied:

Risks to participants are minimized by using procedures consistent with sound research design that do not unnecessarily expose participants to risk.
Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those that may result from the research, as distinguished from those participants would receive even if not participating.
Selection of participants is equitable. The IRB should consider the purposes of the research and the setting in which the research will be conducted and be particularly mindful of the special problems of research involving vulnerable populations. Participants should share equally in foreseeable benefits and risks.
Informed consent is sought, and will be obtained, from each prospective participant or the participant’s legally authorized representative in accordance with, and to the extent required by 45 CFR 46.116.
Informed consent is appropriately documented or appropriately waived in accordance with 45 CFR 46.117.
When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants.
When appropriate, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.

Additionally, when some or all of the participants are likely to be vulnerable to coercion or undue influence (e.g., children, prisoners, persons with impaired decision-making capacity, or economically or educationally disadvantaged persons) additional safeguards are included in the study to protect the rights and welfare of these participants.

What is the definition of risk/benefit analysis?

It is an analysis of the potential risks to participants considered against the potential benefits to the individual or to the research objectives of the study.