In 1998, the Department of Health and Human Services (DHHS 45 CFR 46.110) and Food and Drug Administration (FDA 21 CFR 56.110) regulations were revised with regard to categories of research that may be reviewed by an expedited review procedure. The list of research categories eligible for an expedited review was expanded and clarified.
The following two criteria must be met before a protocol may be considered for an expedited review process:
- The activity must present no more than minimal risk to subjects. The regulatory definition of "minimal risk" is 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; and
- The protocol procedures must be listed as one of the categories in the regulations' list of procedures that qualify for an expedited review process. The research categories that may qualify for an expedited review process are listed below. Additional information may be found at: http://www.hhs.gov/ohrp/policy/exprev.html, http://www.hhs.gov/ohrp/policy/expedited98.html or http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm119074.htm.
The investigator must be aware of the following information regarding expedited research:
- The categories in the expedited research list apply regardless of the age of subjects, except as noted.
- The expedited review procedure may not be used where 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 in terms of 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.
- The expedited review procedure may not be used for classified research involving human subjects.
- The standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.
- Categories one (1) through seven (7) below pertain to both initial and continuing IRB review.
The list of research categories eligible for an expedited review:
(1) Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
(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.)
(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.
(2) 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. 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
(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. 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.
(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.
(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.
(5) 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. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
(6) Collection of data from voice, video, digital, or image recordings made for research purposes.
(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.)
(8) Continuing review of research previously approved by the convened IRB as follows:
(a) 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
(b) where no subjects have been enrolled and no additional risks have been identified; or
(c) where the remaining research activities are limited to data analysis.
(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.
The final decision on whether an expedited review process may by used rests with the IRB.
Human subject research is regulated at the federal, state, and local level. The two principal federal agencies with human research oversight, the Department of Health and Human Services (DHHS) and the Food and Drug Administration (FDA), have promulgated regulations which are not always consistent with one another. The chart below identifies some of the differences between the DHHS and FDA regulations that affect human subjects, investigators and the study team, sponsors, research institutions, funding agencies, and Institutional Review Boards.
Comparison of FDA and HHS Human Subject Protection Regulations.
The Office of Human Research Protections (OHRP) is responsible for the regulatory oversight of human subjects research that HHS supports or conducts or that institutions choose to place under OHRP’s authority.
Each Common Rule department or agency is responsible for oversight of the research that it supports or conducts. Each of them may have its own policies or a slightly nuanced interpretation of certain provisions of the Common Rule that differs from HHS’s interpretations.
For example, if you are receiving funding from the Department of Education for a research study, you would direct your questions about the Common Rule and protecting research participants to the program officers at the Department of Education.
If you have a question or concern about human subjects protections, compliance, or oversight, it is important to ask the department or agency that is supporting your research.
FDA considers the following to be test articles: (boldfaced content is for emphasis)
- Articles that are considered drugs or biologics*, meaning any substance that is described by one of the following:
- recognized by an official pharmacopoeia or formulary;
- intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease;
- (other than food) intended to affect the structure or any function of the body;
- a substance intended for use as a component of a medicine (but not a device or a component, part or accessory of a device).
*Dietary supplements, foods, and other substances may be considered drugs if they are being used to diagnose, cure, treat, mitigate, or prevent a disease or condition. Consult FDA Guidance for more information.
- Articles that are considered devices*, meaning an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is described by one of the following: (boldfaced content is for emphasis)
- Recognized by an official pharmacopoeia or formulary;
- intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease; or
- intended to affect the structure or any function of the body
and
- which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.
Studies that are considered human research typically include:
- Studies involving human subjects to test or design devices, products, or materials developed through research for human use (e.g., testing if interactive virtual reality (VR) experiences using biometric information contribute to individual mindfulness and relaxation).
- Interventions or interactions with individuals to collect data for research purposes (e.g., evaluation of teaching methods and programs, internet surveys about sugar consumption, research involving risky behaviors or attitudes, and open-ended interviews with minors about family values in a foreign country that contribute to generalizable knowledge).
- Studies using private information that can be readily identified with individuals, even if the information was not collected specifically for the study in question.
- Studies that use bodily materials, such as cells, blood, urine, tissues, organs, hair, or nail clippings, even if these were not originally collected for research purposes.
- Studies that intend to produce generalizable knowledge about categories or classes of subjects from individually identifiable information.
- Studies that involve analysis of existing individually identifiable private information.
Use the quick decision tools below that should assist you with determining if your research involves human subjects, may be considered exempt from Federal regulations, or is not considered human subjects research.
OHRP Human Subjects Regulations Decision Charts
NIH Decision Tool: Am I Doing Human Subjects Research?
Projects that involve quality improvement, case reports, program evaluation, marketing and related business analysis, and surveillance activities may not be considered human subject research, so long as the project does not involve
- A systematic investigation designed to develop or contribute to generalizable knowledge using human subjects, or
- A clinical investigation.
The following questions can help an investigator determine if a particular activity is human subjects research and therefore subject to human subjects protection regulations:
- Does the activity involve research according to definitions outlined in the Code of Federal Regulations at 45 CFR §46.102(d)?
- Are human subjects involved as defined in 45 CFR §46.102(f)?
- Does the research qualify for an exemption under 45 CFR §46.101(b)?
- Is the project nonexempt human subjects research supported by the US Department of Health and Human Services (HHS) or otherwise covered by an institution's Federalwide Assurance (the required federal documentation of an institution's commitment to comply with federal regulations and maintain policies and procedures for the protection of human participants)?
The IRB uses the following guidance to determine if a project is or is not human subject research:
IRB must review all projects that meet the definition of research and that involve human subjects prior to any data collection to determine the appropriate level of review, and, as appropriate, approve them. There are three major types of review: Exempt, Expedited, and Full.
Exempt Review
Studies with no more than minimal risk that meet the federal exempt review criteria (e.g., research using anonymous surveys) which are reviewed by the IRB chair or experienced IRB reviewer(s) designated by the chair.
Expedited Review
Studies that involve no more than minimal risk, but which do not meet any of the criteria for exempt status may be eligible for Expedited Review. 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.
Full Review
Studies that are greater than minimal risk or studies that are minimal risk but are not eligible for exempt or expedited review. Full board studies are reviewed by the full, convened IRB with a recorded vote.
Examples of studies requiring full board review:
- Randomized treatment studies
- Studies using investigational drugs and/or devices
- Behavioral studies involving risky interventions, observations of illegal behavior or very sensitive data/questions
What Must the Board Determine?
- The proposed research design is scientifically sound and will not unnecessarily expose subjects to risk
- Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of knowledge that may reasonably be expected to result
- Subject selection is equitable
- Additional safeguards required for subjects likely to be vulnerable to coercion or undue influence
- Informed consent is obtained from research subjects or their legally authorized representative(s)
- Risks to subjects are minimized
- Subject privacy and confidentiality are maximized
For research that is federally funded (45 CFR) and for FDA regulated research (21 CFR), the IRB relies on the respective regulation: 45 CFR 46 Subpart D—Additional Protections for Children Involved as Subjects in Research or 21 CFR 50 Subpart D–Additional Safeguards for Children in Clinical Investigations, in determining whether one or both parents are to sign the consent (permission) form. The IRB may determine that consent (permission) of one parent is sufficient. In making this determination, the IRB considers the research to involve either:
- No greater than minimal risk to children; or,
- Greater than minimal risk but presenting the prospect of direct benefit to individual subjects
In all other cases, the federal regulations require the researcher to obtain consent (permission) from both parents unless the other parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child. These other cases are when the IRB determines the research is:
- Greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects’ disorder or condition; or,
- Not otherwise approvable that present(s) an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.
In all four types of research, the IRB is to find that adequate provisions for soliciting the assent of the children and permission of their parents or guardians are met. As regards the signature for legal guardians*, generally the signature of one legal guardian is sufficient; however, the investigator should be familiar with state or local law requirements that may be more stringent.
The requirement of two parent signatures is intended by the IRB and the federal regulations as an additional safeguard and protection for children and not as an obstruction for researchers.
The regulations state, for the latter two cases of research, that both parents must sign the consent form to enroll the child unless “…one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.”
As there is no regulatory definition for “not reasonably available,”** the investigator must ultimately make the determination that a parent is not reasonably available to be consulted, with respect to parental permission and he/she should document the reasons supporting that decision in the study file.
*21 CFR 50.53(s) Guardian means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.
**Parental Permission in Research involving Children, Focusing on “Not Reasonably Available” SACHRP Recommendation, October 17, 2018
Yes, there is an easy way to add CVs and CITI training to IRBNet. If you create a user profile, you can upload your documents. When you have a new project, you can link your profile documents to the file.
See the instructions for this process here.