IRB Review of Research
This information is based on the Common Rule, current in January 2017. The revisions to these regulations (known as the Final Rule) were published in the Federal Register on January 18, 2017 and go into effect on January 19, 2018. This information will be updated by the effective date of these changes. For now, the following information remains current.
The Institutional Review Board (IRB) reviews and approves human subject research to ensure research is conducted ethically and that the rights and welfare of subjects are protected.
Any project that meets the federal definitions of research with human subjects falls under the scope of Children's Hospital of Wisconsin IRB oversight. These projects must be reviewed by the IRB before any activities begin, and unless also eligible for exemption, the IRB maintains continued oversight of these projects.
With the exception of some special types of projects (HUD, Expanded Access) - if the project does not meet the federal definitions of human subject research, IRB review is not required.
Decision Tree – For help in analyzing whether a project should be submitted for a determination, and/or whether it requires Children's IRB review and approval. If you are unsure after analyzing your project, or have need for an official determination letter from the IRB, the project can be submitted for review. The IRB office can also provide an informal opinion about your project - contact the office for directions.
See also: Am I doing research? NIH Infopath questionnaire – a quick decision tool that should assist you with determining if your research involves human subjects, may be considered exempt from the Federal regulations or is not considered human subjects research.
Additional resources are listed at the bottom of this page.
Both the Office for Human Research Protection (OHRP) and the Food and Drug Administration (FDA) have definitions of human subjects research. OHRP and the FDA are both components of Health and Human Services (HHS), but each has a separate set of regulations governing human subject protection which are consistent with the different missions of each agency.Generally, FDA regulations apply to all research that involves products regulated by the FDA, including research and marketing for:
- Biologic products
- Medical devices for human use
- Food and color additives
- Electronic products
If a protocol is subject to regulations under both agencies, requirements of both must be met.
All research conducted in Children's affiliate facilities that involve children, parents, or staff must be reviewed and approved by the IRB. Scroll down for information on special situations.
Analyzing a project regarding IRB review needed
1. Is this project human subjects research or something else?
- 21 CFR 50.3(c): "Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(j) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions for part 58 of this chapter, regarding nonclinical laboratory studies."
- 21 CFR 50.3(j):"Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act (42 U.S.C. 262 and 263b-263n).
- 21 CFR 50.3 (g):"Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient."
- 21 CFR 812.3 (p):"Subject means a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease."
Move to the HHS (OHRP) definitions (Common Rule) - if the project does not meet the FDA definitions, it may still meet the Common Rule definitions of human subject research. Under the Common Rule, to be human subject research, it must meet both the definition of research, and the definition of human subject.
- 45 CFR 46.102 (d):"Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge."
- 45 CFR 46.102(f):"Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains: (1) data through intervention of interaction with the individual, or (2) identifiable private information."
2. If the project is human subjects research, is it eligible for exemption from the regulations (and thus continued IRB oversight)?
- Sometimes a project may meet the regulatory definitions of human subject research, but also fall under one of the 6 exempt categories 45 CFR 46.101(b). This means that the project is not subject to the regulations, even though it is research. If a project is exempt research, the IRB does not need to maintain oversight (i.e. additional submissions for things like reportable events or continuing review are not required)
- None of the categories apply to research with prisoners or pregnant women
If you think your project may fall under one of these categories, initial IRB submission is required for a final determination that the project is exempt. If the project changes in a way that makes it no longer eligible under one of the exemption categories, it will need to be resubmitted to the IRB.
- Submit the project through IRBNet as a new project, select "exempt" under project type on the registration form
- The IRB will issue a letter of determination (this is not a approval) regarding whether the project is in fact exempt
- Determination the project is exempt:
- IRB will not conduct subsequent reviews (reportable event, continuing review) of the study
- Amendments (changes) to the study should be reviewed by the IRB to determine if the project still meets the criteria for exemption
- Consent is still needed
- Subjects should be told the activity is research
- Subject privacy still needs to be protected. HIPAA privacy rules still apply to all exempt research that uses protected health information
Determination the project is not exempt:
- project will proceed with normal IRB review (expedited or full board as appropriate) and is subject to continued oversight by the IRB (continuing review, reportable event review, etc).
- OHRP decision charts regarding exemption
- Exempt research determinations – FAQs
- Categories of exempt research (45 CFR 46.101 (b) (1-6))
- OHRP guidance – exempt research and research that may undergo expedited review
- Categories of exemption checklist
3. If the project is human subject research, is it eligible for expedited review (for both exempt or non-exempt projects)?
- Expedited review procedures are allowed for certain types of research involving no more than minimal risk, and for minor changes in approved research. This means that rather than being reviewed by the full board at a regularly convened meeting, the review is conducted by an IRB chair, or their designee, outside of the regularly scheduled IRB meetings.
- Expedited does not mean fast. Regulations require that an expedited review be given the same scrutiny that a submission to the full board would receive. Pre-review, modification requests, compliance review all still take place and can take time before approval is granted.
- An expedited reviewer can approve or require modifications, but cannot disapprove a study. Full board vote is required for disapproval.
- The IRB makes the determination whether a project qualifies for expedited review or requires full board review.
- A proposed study that does not meet the requirements for exempt status may still undergo an expedited review it if meets the regulatory criteria for expedited review.
- OHRP (HHS) categories of expedited review. Categories one (1) through seven (7) pertain to both initial and continuing IRB review. Categories eight (8) and nine (9) pertain only to continuing review.
- FDA expedited review (21 CFR 56.110)
- OHRP (HHS) expedited review (45 CFR 46.110)
- ORHP (HHS) decision charts regarding expedited review
- Categories of Expedited Review checklist
There are some activities which, while not research, still require submission to the IRB for review and approval or acknowledgement.
- Humanitarian Use Device (HUD): as defined in 21 CFR 814.3(n) and updated by the 21st Century Cures Act, a HUD is a "medical device intended to benefit patients in the treatment of diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year." (the CFR Regulation still states the population as "fewer than 4,000" however, on December 13, 2016 Section 3052 of the 21st Century Cures Act (Pub. L. No. 114-255) changed the population estimate required to qualify for HUD designation from "fewer than 4,000" to "not more than 8,000.")
- In accordance with FDA regulations 21 CFR 814.124, IRBs are required to approved the use of a HUD, except in emergency situations, in order for an institution to deliver the device to patients.
- An investigator must apply for IRB review and approval before using an HUD at Children's Hospital. These materials should be submitted to the IRB in the same manner as other research protocols.
- In addition to initial approval by the full IRB, IRBs must perform continuing review of a HUD application at least yearly.
- FDA website – designating HUD
- FDA website – HUD exemption
- FDA final guidance – HUD designations
- FDA FAQs – designating HUD
- FDA education and media resources for HUD program
- Children's policy – HUD
- HUD IRB application
- New HUD – reviewer worksheet
Expanded Access (Compassionate Use): Expanded access, sometimes called "compassionate use," is the use outside of a clinical trial of an investigational medical product (for example, one that has not been approved by the FDA). This is considered treatment use, not research, and must be approved by the FDA. The treatment use may be either emergency use or non-emergency use. While the IRB does not need to approve use of the product in addition to the FDA, investigators are required to notify the IRB within certain time limits. There are differences in the use of drugs versus devices under expanded access. See the FDA site for detailed information.
- FDA website – expanded access (compassionate use)
- FDA guidance – expanded access to investigational drugs for treatment use - Q&A
- FDA website – expanded access for medical devices
- Expanded access regulations – 21 CFR 312 subpart 1
- FDA guidance – charging for investigational drugs under an IND – Q&A
- FDA guidance – individual patient expanded access applications: Form FDA 3926
- Guidance and Checklist - Individual Patient Expanded Access
- OHRP decision trees
- OHRP quality improvement activities – FAQs
- OHRP video: back to basics – does my project fall under the scope of the regulations
- Am I doing research? NIH Infopath questionnaire
- Harvard School of Public Health Power Point – blurred lines: QA/QI vs. research
- Quality improvement or research worksheet (Adapted from the Hasting Reports – from the CHOP website)
- SQUIRE website – standards for quality improvement reporting excellence
- Publication guidelines for improvement studies in health care: evolution of the SQUIRE Project