Categories of Review
Applications for approval of research involving human subjects may qualify for one of three levels of review: full-board, expedited or exempt. Before starting an IRB application, investigators must identify the appropriate review type. Investigators are encouraged to contact the IRB Administrator to discuss what review type their protocol falls under.
OHRP Human Subjects Decision Charts provide graphic assistance as a guide for investigators.
Definition of Research
- Chart 01: Is an Activity Human Subjects Research Covered by 45 CFR Part 46?
- Chart 02: Is the Research Involving Human Subjects Eligible for Exemption Under 45 CFR 46.104(d)?
- Chart 03: Does Exemption 45 CFR 46.104(d)(1) for Educational Practices Apply?
- Chart 04: Does Exemption 45 CFR 46.104(d)(2) for Educational Tests, Surveys, Interviews, or Observation of Public Behavior Apply?
- Chart 05: Does Exemption 45 CFR 46.104(d)(3) for Benign Behavioral Interventions Apply?
- Chart 06: Does Exemption 45 CFR 46.104(d)(4) for Secondary Research that Does Not Require Consent Apply?
- Chart 07: Does Exemption 45 CFR 46.104(d)(5) for Public Benefit or Service Programs Apply?
- Chart 08: Does Exemption 45 CFR 46.104(d)(6) for Food Taste and Acceptance Studies Apply?
- Chart 09: Does Exemption 45 CFR 46.104(d)(7), Storage for Secondary Research for Which Broad Consent Is Required, Apply?
- Chart 10: Does Exemption 45 CFR 46.104(d)(8) for Secondary Research for Which Broad Consent Is Required Apply?
- Chart 11: Is Continuing Review Required Under 45 CFR 46.109(f)?
- Chart 12: Waiver or Alteration of Informed Consent in Research Involving Public Benefit and Service Programs Conducted by or Subject to the Approval of State or Local Government Officials (45 CFR 46.116(e))
- Chart 13: When Can Informed Consent Be Waived or Altered Under 45 CFR 46.116(f)?
- Chart 14: Can Documentation of Informed Consent Be Waived Under 45 CFR 46.117(c)?
This type of research represents no more than minimal risks to participants and does not involve special populations. The purpose of this review is to determine if the research is in keeping with the exempt categories as defined by federal regulation and thus exempt from expedited or full-board review. This type of research still requires submission of the protocol to the IRB Administrator and Chair for review and approval of the exemption. The Chair and a designated member of the IRB are authorized to determine if the research qualifies for exemption based upon the federal regulations. Normally, informed consent is not required for exempt research. If the IRB Chair determines that a signed informed consent form is required, the request will be upgraded to expedited or full-board review. Research that falls into one of the categories below may be considered exempt:
- 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.
- 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:
(i) 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;
(ii) Any disclosure of the human subjects' responses 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
(iii) 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 to make the determination required by §46.111(a)(7).
- 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 when certain criteria are met. Note- benign behavioral interventions are 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.
- Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met:
(i) The identifiable private information or identifiable biospecimens are publicly available;
(ii) Information, which may include information about biospecimens, 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;
(iii) The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or
(iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for nonresearch 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. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 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.
- 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 (or the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public 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.
- Taste and food quality evaluation and consumer acceptance studies
- Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB review and makes the determinations required by §46.111(a)(8).
- Secondary research for which broad consent is required: Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if certain criteria are met
Information taken from: 45.CFR.46.101(b)(1-6).
Only members of the IRB may determine that a study is exempt from expedited or full-board review. Once a study is deemed exempt, it will not be required to undergo further review, such as continuing review, unless there are changes to the approved protocol.
In circumstances where there is no more than minimal risk, federal regulations permit the IRB to conduct expedited review. The VCOM IRB may also use the expedited review procedure to review minor changes in a previously approved research during the period for which approval is authorized.
Some studies involving children can be approved under expedited review. The categories for expedited review are the same as in adult studies; however, blood collection limits differ. Research involving collection of protected health information (PHI) that is approved by both the parent and child with appropriate consent and assent forms can use expedited review.
The categories for expedited review are:
- Clinical studies of drugs and medical devices when: (a) Research on drugs for which an investigational new drug application (21 CFR 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 (b) Research on medical devices for which (i) an investigational device exemption application (21 CFR 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.
- Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows: (a) from healthy, nonpregnant adults who weigh at least 110 pounds (Note, amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week); or (b) from other adults and children, considering the 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 (Note, 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 2 times per week).
- Prospective collection of biological specimens for research purposes by noninvasive means. Examples: (a) hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and subgingival 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; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.
- Collection of data through noninvasive 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: (a) physical sensors that are applied either to 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; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.
- Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch 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.)
- Collection of data from voice, video, digital, or image recordings made for research purposes.
- 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. This listing refers only to research that is not exempt.)
Information taken from: OHRP Categories of Research, Expedited Review Procedure
These expedited categories represent minimal requirements of review, and the VCOM IRB may call for a more stringent review of any study. Expedited Review may be carried out by the IRB Chair and a member of the IRB or by two IRB members designated by the Chair. When conducting an Expedited Review, IRB members may exercise all of the authorities of the IRB, except that the reviewer(s) may not disapprove the research. A research activity may be disapproved only after a full IRB review has been conducted. All IRB members must be advised of research proposals that have been approved using expedited procedures at the next regularly scheduled meeting.
Full-board review by the entire IRB committee is reserved for studies that have potential risk to human subjects. All research that does not meet the criteria for exempt or expedited review will be reviewed by the full Board at a regularly convened meeting. For the research to be approved, it must receive the approval of a majority of those members present at the meeting. If the IRB Chair has any concerns about any aspect of the application, he may request full IRB review of any application even though it may otherwise qualify for exemption or expedited review. Potential risks to human subjects that would warrant full-board review include, but are not limited to:
- Research that involves the administration of drugs or other substances to subjects where an IND/IDE are required.
- Research that materially affects the pregnancy of a woman or the health/well-being of fetuses in utero.
- Research involving subjects with life-threatening physical conditions.
- Research involving physically intrusive procedures.
- Research that previous experience (by the particular investigator or other investigators) has been shown to create a potential of risk to subjects.
- Research that may result in a significant level of psychological or physical stress.
- Research that potentially could put the subject at risk for legal or civil liability or invade a subject's privacy in regard to sensitive aspects of his/her behavior (e.g., illegal conduct, drug use, sexual behavior, alcohol use) when there is a possibility that the subject could be identified.
- Research involving prisoners.
- Research that places protected populations (such as children, mentally ill individuals, patients with medical disorders) at more than minimal risk.
- Research involving waivers of any HIPAA regulations.
- Research that is not conducted for the primary benefit of the subjects.
- Deception or procedures that are not known to the subject (e.g., the subject will not be fully informed about study objectives).
Investigators with applications under full-board review may be present at the IRB meeting covering their protocol in order to answer questions posed by IRB members. Attendance at these meetings is optional, unless otherwise indicated by the IRB Chair, and should be scheduled with the IRB Administrator at least three weeks prior to the designated meeting.
Under the revised Common Rule, continuing review is not required for:
- Research that is eligible for expedited review,
- Exempt research conditioned on limited IRB review,
- Research that has completed all interventions and now only includes analyzing data, even if the information or biospecimens are identifiable,
- Research that has completed all interventions and now only includes accessing follow-up clinical data from clinical care procedures.
Importantly, the IRB can override this default and still choose to require continuing review, as long as the IRB documents the decision and the rationale for this decision.
[Refer to 45 CFR 46.109(f), 46.110, and 46.115(a)(8) of the revised Common Rule.]
Note- Non-exempt studies reviewed under the pre-2018 Common Rule must still undergo yearly continuing review.
Research involving outside Institutions (Collaborative Research)
Research may be undertaken through the collective efforts of many individuals, and often results in researchers working together from different academic institutions or clinical facilities. It is increasingly common for multiple institutions to work together on projects. Such collaborative research can pose many ethical challenges, largely because of the number of people, institutions, and resources involved. Care should be taken when undertaking collaborative research as an Institutional Authorization Agreements (i.e., IAA or reliance agreements) may be required between collaborative institutions prior to initiating research. More information regarding collaborative research and reliance agreements can be received by contacting IRB administration at firstname.lastname@example.org.
Other Populations Requiring Special Consideration:
While there are currently no specific federal regulations that address the needs of these populations, the VCOM IRB will carefully consider projects that involve any of the following groups:
- Mentally disabled persons;
- Economically or educationally disadvantaged persons; and
- Students, employees and others in subordinate positions.
Every project reviewed by the VCOM IRB is evaluated for circumstances that may place participants in vulnerable situations. When the IRB deems a group as being vulnerable in a particular research project, the committee will consider whether the protocol provides adequate protections and may require additional protections as a condition of approval.
Mentally disabled persons are those who have a diminished capability for judgment and reasoning due to developmental, psychiatric, organic or other disorders that affect cognitive functions. The VCOM IRB holds that research involving mentally disable persons should not be done if:
- The research questions could be answered by involving capable persons or
- More than minimal risk is involved (unless the research holds out direct benefit to the subject)
Furthermore, research that must involve this population must include safeguards that show decision making capacities will be tested and documented in the study. The investigator must provide thorough justification on why such a population is the only appropriate one for the research, and must detail how adequate informed consent will be obtained.
The Department of Health and Human Services has available FAQs on involving mentally disabled persons in research:
- When may a legally authorized representative provide consent on behalf of an adult with diminished decision-making capacity?
- What should be considered in seeking informed consent from individuals with diminished decision-making capacity?
Economically or educationally disadvantaged persons may also require special protections in a research environment. When such groups are targeted specifically as research subjects, the IRB will ensure adequate safeguards are in place to protect such individuals.
- For research involving economically disadvantaged participants, care must be taken to assure that any financial incentives offered do not represent the only grounds for the individual’s participation in the research protocol.
- Financial incentives should also not be used to encourage participants to assume risks that they would not ordinarily incur.
The consent form for research involving educationally disadvantaged participants must be written in language appropriate to the participant. In some cases, the investigator must discuss orally every aspect of the study with the participant to insure participant understanding.
The Department of Health and Human Services FAQs include insights into situations involving economically or educationally disadvantaged persons:
- What does it mean to minimize the possibility of coercion or undue influence?
- When does compensating subjects undermine informed consent or parental permission?
- How can the consent and parental permission process be designed to facilitate understanding?
Students, employees and others in subordinate positions can feel unduly influenced to participate. In many studies, students are recruited as participants; however, investigators should be aware of possible coercion when involving students in their research. If students believe their participation (or lack of) will be made known to someone involved in his or her academic status, the student may perceive coercion. This also holds true for employees and others at VCOM who may be in subordinate positions.
If an investigator is planning to involve students or employees in a research study, the potential problems of coercion and undue influence must be addressed in the application. In particular, activities that involve students who attend a class the investigator teaches or employees who report directly to the investigator must be disclosed and explained. The IRB will consider whether the autonomy and confidentiality of these individuals are protected. Such considerations include:
- Incentives for participation do not present undue influence;
- Participants have the ability to decline participation;
- Confidentiality is maintained for self-disclosures of a personal nature;
- If course credit is given for participation, alternatives no more burdensome than the research participation are available for receiving equal credit.
Department of Health and Human Services FAQs raise questions for consideration when involving students and others in subordinate roles in research:
- What does it mean to minimize the possibility of coercion or undue influence?
- What constitutes coercion or undue influence when students are involved in research in a college or university setting?
- What constitutes coercion or undue influence when employees are the subjects of research?
The following links are to federal resources that describe the requirements dictating vulnerable subject participation in research and the steps investigators should take to ensure all safeguards are met.
OHRP video, Research Involving Vulnerable Populations: YouTube video (28 minutes).
OHRP’s guidance: Special Protections for Children as Research Subjects
ORRP FAQs on Research with Children
OHRP FAQs on Prisoner Research
NIH guidance on Research Involving Vulnerable Populations - Children
NIH guidance on Research Involving Vulnerable Populations - Prisoners
Frequently, programs are presented at area institutions that are aimed at research involving human subjects, confidentiality and other ethical concerns for researchers. The IRB Administrator will inform deans and discipline chairs of upcoming events, so this information can be disseminated to faculty and students at VCOM who may be interested in attending.
If you have any questions on training opportunities, please contact the IRB Administrator.