The Review Process

The only exemption that may be applied to vulnerable populations (e.g., prisoners, children) is Category 1. All other research with vulnerable populations requires at least expedited review and ongoing oversight by the IRB.

Research involving the use of deception does not qualify for exempt status.

Category 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.

Examples:

• Evaluating the effectiveness of a new approach to teaching
• Testing or comparing a curriculum or lesson
• Evaluation of the effectiveness of a teacher training program

Category 2

Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior if at least one of the following criteria is met:

1. The information obtained is recorded by the investigator in such a manner that the identity of the human participants cannot be readily ascertained, directly or indirectly through identifiers linked to the participants; OR
2. Any disclosure of human participants’ responses outside the research would not reasonably place the participants at risk of criminal or civil liability or be damaging to the participants’ financial standing, employability, educational advancement, or reputation.

Examples:

• Surveying college students about their attitudes about a particular social issue
• Interviewing managers about a management style or best practice
• Conducting a focus group about an experience or an opinion of a community program

Category 3

Research involving benign behavioral interventions in conjunction with the collection of information from adult participants through verbal or written responses (including data entry) if the participants prospectively agree to the intervention and information collection and at least one of the following criteria is met:

1. The information obtained is recorded by the investigator in such a manner that the identity of the participants cannot readily be ascertained, directly or indirectly, through identifiers linked to the participants; OR
2. Any disclosure of the participants’ responses outside the research would not reasonably place them at risk of criminal or civil liability or be damaging to their financial standing, employability, educational advancement, or reputation.

For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the participants, and the investigator has no reason to think the participants will find the interventions offensive or embarrassing. Provided all such criteria are met, examples of such benign behavioral interventions would include

Examples:

• Participants play an online game
• Participants solve puzzles under various noise conditions
• Participants decide how to allocate a nominal amount of received cash between themselves and someone else.

Category 4

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:

1. The identifiable private information or identifiable biospecimens are publicly available; OR
2. 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; OR
3. 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 (HIPAA), 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).

Note: Exemption Category 4 only applies to the re-use of data and specimens that were or will be collected for non-research purposes or from research studies other than the proposed research study. The research materials typically will be publicly available materials, medical records, or existing repositories of clinical specimens. No contact between investigator and subjects is allowed. If an investigator wants to collect information/specimens directly from research subjects, then another IRB review path will be required. Exemption Category 4(iii) only applies to the use of data (when HIPAA applies) and not to biospecimens.

Example:

• A researcher is given two datasets that contain private, identifiable information. The researcher uses the identifiers to merge the two datasets but strips the resulting (merged) data of identifiers immediately after the merge and before conducting data analysis. The resulting data used for the analysis is completely de-identified with no link to identifiers.

Category 5

Research and demonstration projects which 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 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.

Each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible Federal Web site or in such other manner as the department or 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 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 Department of Agriculture.

Categories one (1) through seven (7) pertain to both initial and continuing IRB review. Categories eight (8) and nine (9) pertain only to continuing IRB review.

Category 1

Clinical studies of drugs and medical devices if at least one of the following criteria is met:

1. 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.

Category 2

Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

1. 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, 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.

Category 3

Prospective collection of biological specimens for research purposes by noninvasive means.

Examples:

• hair and nail clippings in a nondisfiguring 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 gumbase or wax or by applying a dilute citric solution to the tongue;
• 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;
• mucosal and skin cells collected by buccal scraping or swab, skin swab, nasal swabs that do not go beyond the nares, or mouth washings;
• sputum collected after saline mist nebulization.

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:

• 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 subjects 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 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).

• Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4).
• This category includes materials that were previously collected for either non-research or research purposes, provided that any materials collected for research were not collected for the currently proposed research.
• The phrase “…or will be collected solely for non-research purposes” pertains to the origin of the materials. For example, blood samples that were collected for a clinical test or the results of a course driven exam given in a history class.

Category 6

Collection of data from voice, video, digital, or image recordings made for research purposes.

Note: Expedited Review does not apply if identification of the participants and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to their financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

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).

If the research involves the use of deception, it may require review by the full IRB (see guidelines regarding the use of deception [see here]).

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 participants; (ii) all participants have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of participants; or
2. where no participants have been enrolled and no additional risks have been identified; or
3. where the remaining research activities are limited to data analysis.

Clarifiers regarding condition (1):

• Closure of enrollment only has to apply to the local site, not to all sites,
• Long-term follow-up may include research interactions (as opposed to intervention) that involve no more than minimal risk to participants (e.g., quality of life surveys);
• Long-term follow-up may include collection of follow-up data from procedures or interventions that would have been done as part of routine clinical practice to monitor a participant for disease progression or recurrence, regardless of whether the procedures or interventions are described in the research protocol.

Clarifiers regarding condition (2):

• “no participants have been enrolled” means no participants enrolled at the local site
• “no additional risks have been identified” means no additional risks identified at the local site or any other institution engaged in the research project or from any other relevant source since the IRB’s most recent prior review.

Clarifiers regarding condition (3):

• The only remaining human participants research activity is the analysis of data that includes identifiable private information and the IRB reviewer has determined that this activity involves no more than minimal risk.
• Simply maintaining individually identifiable private information without using, studying, or analyzing such information is not human participants research and thus does not require continuing review.