SACHRP Recommendations on Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure under the Revised Final Rule
Research that involves one or more of the following categories and is evaluated to be no more than minimal risk may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110. A study is presumed to be minimal risk and thus eligible for expedited review if the study only involves categories described in this document, unless the reviewer determines and it is documented why the study involves more than minimal risk (§__.115(a)(8)).
The criteria for IRB approval of research as stipulated in 45 CFR 46.111 and 21 CFR 56.111, including but not limited to requirements for informed consent and documentation of informed consent, as applicable, apply when expedited review procedures are used by the IRB.
Under an expedited review procedure, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB.
Evaluating if Proposed Activities are No More than Minimal Risk
Most research falling within one or more of the categories below will, ordinarily, present no more than minimal risk to subjects and will be eligible for review through the expedited review procedure. However, the IRB reviewer is required to evaluate all proposed research and consider whether the proposed research is more than minimal risk.
In evaluating if the proposed research presents no more than minimal risk, an IRB reviewer should consider the nature of the study procedures, the implications of study findings for the subject (e.g., the results of genetic testing of blood samples), other study characteristics, and steps taken to minimize risk. The IRB reviewer should also consider the characteristics of the subject population, including but not limited to age, health conditions, social or economic circumstances and experience in relation to the anticipated harms and discomforts.
The expedited review procedure may not be used, for example, when identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, insurability, reputation, educational advancement, 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. In evaluating the risks, the IRB reviewer should consider only those risks that may result from the research (as distinguished from the risks of therapies subjects would receive even if not participating in the research).
A. Categories one (1) through fourteen (14) apply to initial IRB review of research that has been determined to be no more than minimal risk.
B. Category fifteen (15) applies to continuing review of research previously approved by the convened IRB that does not otherwise qualify for expedited review.
C. The categories in this document apply regardless of the age of subjects, except as noted.
D. Research eligible for expedited review under §__110(b)(1)(i) must fit within one or more of the categories below.
E. Examples are intended to suggest the types of research activities and procedures that pose no more than minimal risk and may be approved using expedited procedures. However the applicability of the category is not limited to the specific examples provided.
F. The expedited review procedure may not be used for classified research involving human subjects.
G. Unless an IRB determines otherwise, continuing review of research is not required for research eligible for and approved by expedited review in accordance with §__.109(f)(1)(i).
1. Research involving the use of drugs and medical devices only when condition (a) or (b) is met.
a. Research involving use of “over-the-counter” drugs, when used within their approved indications and dosages, and exempt from the IND requirements of 21 CFR 312.
b. Research involving use of medical devices exempt from the IDE requirements of 21 CFR 812.1
2. The collection of blood specimens for research purposes using techniques consistent with routine clinical practice to minimize pain and risk of infection and within the following limits: (a) from adults whose health will not be adversely affected by the blood draws who weigh at least 50 kg, the amounts collected should not exceed 550 ml in an 8-week period; or (b) from children2 and other adults whose health will not be adversely affected by the blood draws, the amounts collected should not exceed the lesser of 150 ml or 3 ml per kg in an 8-week period. Examples: Finger stick, heel stick, ear stick, venipuncture, collection of blood from an indwelling peripheral venous catheter (not including a PICC line) placed for research purposes, or collection of blood from an indwelling catheter already in place for clinical purposes.
3. Prospective collection of biological specimens, excluding blood, for research purposes by noninvasive means and not requiring sedation for research purposes.
Examples: (a) tissues and fluids that the body produces continuously or sheds as a normal process (including hair, nails), which are collected in a non-disfiguring manner; (b) deciduous teeth at time of exfoliation; (c) excreta and external secretions (including sweat, urine, stool); (d) uncannulated saliva; (e) placenta removed at delivery; (f) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (g) 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; (h) mucosal and skin cells collected by buccal scraping or mouth washings; (i) sputum collected after saline mist nebulization
4. Prospective collection of biological specimens, excluding blood, for research purposes by minimally invasive means and not requiring sedation for research purposes.
Examples: (a) tissues from non-facial, non-genital skin punch biopsy with allowable local anesthesia and limited to 2mm in diameter and not requiring sutures; (b) Specimens collected by swab (nasal, oral, urethral, vaginal, rectal); (c) teeth if routine patient care indicates a need for extraction.
5. Collection of additional information or biological specimens, excluding blood, for research purposes during procedures already being performed for clinical purposes, provided the additional collection does not introduce more than a minimal increase in risk, pain or discomfort over that imposed by the underlying procedure. When extension of general anesthesia is required, it must meet the criteria for minimal risk. 3
Examples: (a) collection of additional bodily fluids and tissues (e.g., peritoneal fluid, bone marrow or cerebrospinal fluid); (b) tissue collected from pap smears; (c) collection of additional clinical information (e.g., vital signs, electroencephalography or echocardiography).
6. Collection of information for research purposes through noninvasive procedures and interventions routinely employed in clinical practice and not requiring general anesthesia or sedation.
Examples: (a) physical sensors that are applied either to the surface of the body or used at a distance; (b) testing sensory acuity; (c) magnetic resonance imaging without use of contrast agent and using magnet and sequence parameters within accepted clinical use guidelines; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, Doppler blood flow, and transthoracic echocardiography; (e) measures of cognitive functioning; (f) exposure to ionizing radiation with a total effective dose not exceeding 0.1 mSv (the amount typically associated with a single chest x-ray) provided appropriate shielding techniques are employed.4
7. Collection of information for research purposes through activities performed by persons in daily life in individuals and groups whose health will not be adversely affected by the activities.
Examples: (a) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing; (b) measures of symptoms, mobility, range of motion, quality of life and activities of daily living in patient and non-patient populations by clinical or other trained personnel (e.g., nurses, physicians, social workers, physical and occupational therapists); (c) manipulations of diet and lifestyle; (d) measuring height, weight, circumference; (e) assessment of reading levels.
8. Activities at statistical and data coordinating centers or biospecimen repositories that are not responsible for the primary oversight of the primary data collection activities and are not involved in the primary collection of information or specimens, which may be ongoing at other sites.
9. Collection of information from voice, video, digital, or image recordings made for research purposes that are not exempt under §__.104(d).
10. Research that only includes interaction involving (1) educational tests (cognitive, diagnostic, aptitude, achievement); (2) survey procedures, interview procedures, or observation of public behavior (including visual and auditory recording) not eligible for exemption under §__.104(d)(2) either because there are risks to subjects other than informational risks, or because the informational risks are not addressed as specified under §__104(d)(2)(i) through (iii); (3) other data collection procedures (e.g., written or computer-assisted interactions or assessments) where the subject provides self-reports for the purposes of the research and/or may choose what data to provide; (4) non-invasive physical or behavioral tasks or manipulation of the subject’s environment; and (5) observations of individual group behavior where the subject is a voluntary participant in the behavior and is aware that data are being collected.
11. Benign behavioral interventions that are not eligible for exemption under §__.104(d)(3) because they (a) involve children as subjects; (b) involve individuals with impaired decision-making capacity; (c) are conducted without the prospective agreement of the subject, including interventions involving deception; (d) are not brief in duration, or; (e) are not limited to verbal or written responses by the subject, data entry by the subject, or observation of the subject.
12. Creation and maintenance of subject databases to which subjects have provided prospective informed consent or informed consent has been waived by an IRB and does not qualify for exemption under §__.104(d)(7). Examples: (a) collection of identifiable information for the purpose of establishing subject pools; (b) disease-specific patient registries; (c) screening protocols including interviews, questionnaires and minimally invasive physical assessments, when performed for research purposes, that could not be expedited under one of the categories listed above.
13. Secondary research uses of identifiable private information or identifiable biospecimens that are not exempt under §__.104(d)(4) because (a) the identifiable private information or identifiable biospecimens are not publicly available; (b) information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of human subjects can be readily ascertained directly or through identifiers linked to the subjects, or the investigator intends to contact the subjects or will re-identify subjects; (c) research use of identifiable health information not regulated under 45 CFR parts 160 and 164, subparts A and E.
14. Research involving the use of identifiable private information or identifiable biospecimens for secondary research use that is not exempt under §__.104(d)(8) because the investigator includes returning individual research results to subjects as part of the study plan.
Continuing Review of Previously Approved Research
15. Research previously approved by the convened IRB and not otherwise eligible for expedited review under categories (1) through (13) above, where one of the following conditions apply:
a. the research remains active only for long-term follow-up of subjects;5 or
b. no subjects have been enrolled at sites under the purview of the reviewing IRB and no additional risks have been identified; or
c. the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk (including, when applicable, a non-significant risk (NSR) determination was initially made by a convened IRB for research involving investigational medical devices), and no additional risks have been identified. In such cases, the exemption from further continuing review at §109(f)(1)(i) does not apply.
1 In research involving the use of investigational devices that require a non-significant risk (NSR) determination, the determination should be made by the convened IRB. Continuing review of research where the FDA or the IRB has determined that a device is NSR may be eligible for continuing review under category 10(c).
2 Children are defined in the HHS [45 CFR 46.402(a)] and FDA [21 CFR 50.3(o)] regulations as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted."
3 Extension of anesthesia time may be considered minimal risk when: the extension of anesthesia time is limited to no more than 15 minutes; the appropriate level of anesthesia has been achieved and the patient is determined to be clinically stable by an anesthesiologist uninvolved in the research protocol; the method/mode of anesthesia to be used is determined not by the research protocol but is in accordance with current standard clinical practice; the same anesthetic agents are utilized for the extension of time required for research; the same clinical care team responsible for administering and monitoring the anesthesia remain with the subject during the research procedure, and; the same level and frequency of monitoring will be maintained throughout the research procedures.
4 The US Nuclear Regulatory Commission’s allowable annual exposure to individual members of the public is 0.1 rem (1 mSv) per year. 10CFR20.1031(a)(1) https://www.nrc.gov/reading-rm/doc-collections/cfr/part020/part020-1301.html
5 No continuing review is required for research that has progressed to the point that it involves only one or both of the following, which are part of the IRB-approved study: (A) Data analysis, including analysis of identifiable private information or identifiable biospecimens, or (B) Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care. (45 CFR 46.109(f)(1)(iii))