Types of Review

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Overview

The Office for Human Research Protections (OHRP) provides decision charts as a guide for institutional review boards (IRBs), investigators, and others who decide if an activity is research involving human subjects that must be reviewed by an IRB under the requirements of the U.S. Department of Health and Human Services (HHS) regulations at 45 CFR part 46.

Human Subject Regulations Decision Charts  (1-11) (HSS.gov)

Note: a determination must be made prior to initiation of research or the activity; it cannot be made retroactively.

Vulnerable Populations

Check Your Study For Vulnerable Populations. See Policies and Guidance for more information.

  • Children
  • Cognitively Impaired Persons
  • Decedent Research Involving Health Information of Deceased Individuals (HIPAA)
  • Elderly / Aged
  • Non-English Speakers
  • Pregnant Women, Fetuses, and Neonates
  • Prisoners
  • Students & Employees

Risk Types

Human subject research governed by Federal regulations falls into one of two categories: Minimal risk or Greater than minimal risk.

  1. Definition of Minimal and Greater Than Minimal Risk: 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.” Note that federal regulations only define minimal risk (45 CFR 46.102(i); 21 CFR 56.102(i)). Therefore greater than minimal risk could be defined as anything determined to be above minimal risk.
  2. Definition of Minimal Risk With Prisoners: Note that minimal risk is defined slightly differently when the research involves prisoners as subjects: minimal risk is then defined as “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)).

Review Types

  1. Exempt Review
  2. Expedited Review
  3. Full-Board Review

* Non-Human Subject Research (NHR) Determinations are only made by the IRB. They must be submitted to the IRB for confirmation as NHR.

Exempt Review

Exempt Review means the research falls under the 6 categories of human subjects research that are exempt from the other provisions of the regulations. The regulations found in 45 CFR 46.101 have determined that the following six categories of research are eligible for exemption status, [45 CFR 46.101(b)]: This review type does NOT mean that IRB Approval is not required.

Additional HIPAA Requirements That Indirectly Impact The Review Of Exemption Status: The Privacy Rule is a Federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996. [45 CFR 160 and 164]. If an IRB has been given the responsibility to consider HIPAA in research issues and if the research potentially falls under the purview of HIPAA, an IRB will be applying not only the 45 CFR 46 exemption categories but also determining if HIPAA applies.

HIPAA applicability requirements vary compared to the DHHS exemption requirements. A research project that is exempt from the human research subject IRB requirements may not be exempt from HIPAA provisions. A project that is not exempt from IRB might be exempt from HIPAA. See the DHHS OHRP Guidance on Research Involving Coded Private Information or Biological Specimens, and the NIH and guidance entitled Institutional Review Boards and HIPAA Privacy Rule.

Under current federal regulations, any study approved under Exempt procedures does not have an expiration date of its IRB approval. There are times when you are required to follow-up with the IRB with your project, please see the After IRB Approval Section at bottom of linked webpage.

When Review of Exemption Status is Not Appropriate: According to the DHHS regulations 45 CFR 46, research involving the following are not appropriate for exemption: 1) Prisoner; 2) Surveying or interviewing of children; 3) Observations of public behavior of children when the investigator(s) participates in the activities being observed.

Exempt Review Categories

Exempt Category 1
 
Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
Exempt Category 2
Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and
(ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.
 

Note: The federal regulations specify that the exemption for survey or interview procedures to not apply to research with children. In addition, the federal regulations specify that the observation of public behavior procedure does not apply to research involving children, except when the investigator does not participate in any of the activities being observed.

Exempt Category 3
Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if:
(i) the human subjects are elected or appointed public officials or candidates for public office; or
(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
Exempt Category 4
Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
 
Note: According to the Office for Human Research Protections (OHRP), exempt reviewer(s) should define "Existing" to mean collected (that is, on the shelf) prior to the research for a purpose other than the proposed research. It includes data or specimens collected in research and non-research activities.
Exempt Category 5
Research and demonstration projects which are conducted by or subject to the approval of Department or Agency heads, and which are designed to study, evaluate, or otherwise examine: +  (Additional Clarification)
(i) Public benefit or service programs.
(ii) Procedures for obtaining benefits or services under those programs.
(iii) Possible changes in or alternatives to those programs or procedures.
(iv) Possible changes in methods or levels of payment for benefits or services under those programs.
 
Note: Department or Agency head means the head of any Federal Department or Agency and any other officer or employee of any Department or Agency to whom authority has been delegated.
Exempt Category 6
Taste and food quality evaluation and consumer acceptance studies,
(i) if wholesome foods without additives are consumed or
(ii) if a 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 or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

 

Expedited Review

Expedited review means that the review can be completed by a qualified IRB reviewer rather than at a convened IRB meeting.
 
Federal Regulations establish nine categories that IRBs may use to invoke the expedited review process. Institutions may adopt some or all of the categories when determining if a research activity can be appropriately reviewed by an expedited review process. Categories 1 through 7 pertain to both the initial and to the continuing IRB review. Categories 8 and 9 pertain only to continuing review. The 9 categories are listed below. Follow the hyperlinks for more details about each category. Hyperlinks will open in a new browser window. Close the new window to return here.
 
The Federal Regulations establish two main criteria for an expedited review. They are:
  1. The research may not involve more than "minimal risk". "Minimal risk" means 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." ([45 CFR 46.102(i)] and [21 CFR Part 56.102(i)])
  2. The entire research project must be consistent with one or more of the following federally defined categories (quoted from the OHRP, the IRB oversight agency, guidance document on Expedited Reviews.)

Some institutions/IRBs have additional requirements. Check with your IRB office for more information about how expedited review is handled by your IRB.

Expedited Review Categories

Expedited Category 1
Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
  1. (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.)
  2. 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.
Expedited Category 2
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
  1. (a) from healthy, nonpregnant adults who weigh 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 2 times per week; or
  2. from other adults and children [2], 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. 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 2 times per week.
Expedited Category 3
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.

Expedited Category 4
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.

Expedited Category 5
Research involving data, documents, records, or specimens that: 1) Have been collected. or 2) Will be collected solely for non-research purposes (such as for medical treatment or diagnosis).

Note: Some research in this category may be exempt from the DHHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.

Expedited Category 6
Collection of data from voice, video, digital, or image recordings made for research purposes.
Expedited Category 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. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)
Expedited Category 8
Continuing review of research previously approved by the convened IRB as follows:
  1. where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
  2. where no subjects have been enrolled and no additional risks have been identified; or
  3. where the remaining research activities are limited to data analysis.
Expedited Category 9
Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

 

Full-Board Review

Fully-Convened Board Review
Full committee review or review by the convened IRB is the standard type of review described in the Federal regulations. It must be used for the initial review of all studies that are not eligible for expedited review or exemption, and research involving prisoners.