Research which involves human subjects can be divided into three categories based on the level of review that is required by the federal regulations. The final decision about the level of review that a particular project requires rests with the IRB. When questions are raised about whether an activity is research involving human subjects the IRB is responsible for making this determination. The IRB (and/or the institution) may choose to impose stricter standards than those required by the regulations and may require that any project receive a higher level of review than their guidelines specify. Regardless of the review procedure employed, the IRB must notify investigators and the institution (in writing) of its decision to approve or disapprove the proposed research activity, or of modifications required to receive IRB approval of the research activity.
If a research project is disapproved, the notification must include a statement of the reasons for the decision and give the investigator an opportunity to respond in writing or in person.
When specific modifications to a protocol or consent form are required by the IRB, the authority to give final approval, subject to satisfactory modification, may be delegated to the Chairperson or another IRB member. “Specific modifications” means that the chair or other IRB member is merely confirming that the required change has been made. It does not include situations in which the chair or other IRB member must use judgment to determine whether the change is appropriate. Authority to approve a study pending a change such as, “add the risks associated with drug X to the risks section of the consent form” cannot be delegated. Authority to approve a study pending a change such as, “include a statement in the risks section of the consent form that one in one hundred persons who have taken this medication have suffered from moderate to severe headaches”, may be delegated.
Federal Exempt -
Within DMH must receive an expedited or full board review.
Research which falls within the following categories is exempt under the Department of Health and Human Services regulations for the protection of human subjects. However, as a matter of policy all exempt category research within DMH must be reviewed by an IRB as if it were covered by the DHHS regulations (an expedited procedure may be used).
The Director of an institution or his authorized representative (usually the IRB) shall determine whether research falls within the exempt categories and is therefore eligible for expedited review. However, the Director and/or the IRB may require that a particular project or category of exempt research receive a review by the IRB at a convened meeting.
Exempt categories: 45 CFR 46.101(b)1 (must receive at least an expedited review)
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.
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 subject's 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.
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 item 2 above, 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.
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.
Research and demonstration projects which are conducted by or subject to the approval of federal department or agency heads (including the Department of Health and Human Services), and which are designed to study, evaluate, or otherwise examine:
(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; or
(iv) possible changes in methods or levels of payment for benefits or services under those programs.
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.
Additional categories may be published from time to time in the Federal Register and this manual will be updated accordingly.
1Note: for research involving children, exemption 2 does not apply except for research involving observations of public behavior when the investigator does not participate in the activities being observed.
The expedited review procedure may be used for research which involves only procedures listed within the categories listed below andinvolves no more than minimal risk. This review process may also be used to review minor changes in previously approved research during the period for which the approval is valid, and research which falls within the exempt categories listed above.
An expedited review shall be carried out by the IRB chairperson and/or by one or more experienced reviewers designated by the chairperson from among the members of the IRB. Many IRBs have elected to use two or three reviewers for this type of review. Some IRBs use both a scientific and a non-scientific reviewer to help ensure that the consent form is written in such a way that a non-scientist subject can clearly understand what is involved.
Members conducting an expedited review may exercise all of the authorities of the IRB except that they cannot disapprove a research project. If the reviewer(s) is not willing to approve the project, it must be referred to the full board. If the reviewer has any doubts about the project, he/she should consult with the Chairperson of the IRB and, if doubts remain, refer the project to the full board for review. An expedited reviewer, or any other member of the IRB, may refer a study to the full board for review for any reason.
When an expedited review procedure is used, the IRB must adopt a procedure which will inform the IRB as a whole of the decisions that have been made. Each expedited approval must be documented in the minutes of the following IRB meeting (an attachment is acceptable).
Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure
Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the following categories, or one or more of the federal exempt categories, may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110. The activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects. The risk level associated with a particular procedure commonly varies according the subject population. For example, a single blood draw may exceed minimal risk in medically vulnerable persons or persons with needle phobia.
The categories in this 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 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.
IRBs are reminded that the standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review, expedited or convened (full board) review, utilized by the IRB.
Categories one (1) through seven (7) pertain to both initial and continuing IRB review. Categories eight (8) and nine (9) apply to continuing IRB review.
Research Categories Eligible for 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, non-pregnant 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 non-invasive means.
Examples: (a) hair and nail clippings in a non-disfiguring 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 non-invasive 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 non-research 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 3; 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.
All other research involving human subjects is subject to IRB review at a convened meeting at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. In order for a project to be approved, it must receive the approval of a majority of the members present. When clinical research is being reviewed, at least one physician must be present. When behavioral research is reviewed at least one Ph.D. level behavioralist must be present. Attendance of the non-affiliated member(s) is strongly encouraged.
It is highly desirable to receive comments from members who are unable to attend a meeting. However, except as specified below, members must be physically present at a meeting in order to be counted towards the establishment of a quorum, or to have their "vote" counted. Video-conferencing is permitted by both OHRP and FDA. Participation of a member by conference call is permitted under special circumstances but should not be routinely used. For example, if a special IRB meeting is required to review a report of a serious adverse event or a protocol amendment that is intended to meet the clinical needs of subjects before a sufficient number of members can physically meet, a member who cannot get to the meeting site can participate by conference call. All members, including the person(s) participating via conference call must be provided with the appropriate documentation.
Many IRBs have developed a system whereby one or two members are assigned as primary reviewers for each research project. The reviewers are then responsible for presenting a detailed evaluation of the research to the IRB. All members must be given a copy of the documentation for the application (protocol, consent form etc.) and may participate fully in the IRB deliberations.