Main navigation | Main content
Institutional Review Board review is an ongoing process, not a one-time step. Regular reevaluation ensures that research is conducted responsibly. Even in responsibly conducted studies, a one-time review is inadequate, since risks can really be understood only after research has begun, and since the regulations for human subjects research are constantly being refined as the risks and benefits are better understood. Unexpected developments in a project can raise questions about the conduct of the research, and new findings can raise questions about the project.
"Continuing review" refers to regularly scheduled complete reappraisals of a project. The goals of continuing review are to ensure that the risk/benefit ratio is still acceptable, that the measures taken to safeguard subjects are adequate, that the approved protocol is followed, and that the project reflects any changes that have been made in the regulations for human subjects research since the last approval.
The IRB may require changes in protocol or revisions in the consent form if the study's risks were originally underestimated , but the converse can also occur: the investigators and the IRB may have underestimated the benefit to research subjects.
The Department of Health and Human Services (DHHS) Regulations 45 CFR 46, require that "an IRB shall conduct continuing review covered by this policy at intervals appropriate to the degree of risk, but not less than once per year..." This continuing review must be substantive and meaningful.
A notice for renewal and a "continuing review form" are sent to the principal investigator eight to ten weeks before the review date. The form should be completed and returned to the HRPP office by the indicated deadline. The study expiration date is crucial for the continuation of the study. If the study is allowed to expire, all data collection must cease and no funds may be spent. Any lapses in approval for the use of human subjects must be defended to the IRB and to regulatory or funding agencies. A new application and review will be required to reinstate the study if it expires.
If the investigator does not respond to the final notice, the IRB will classify the study as "inactive."
The IRB is required to report all federally funded studies inactivated due to lack of response to requests for continuing review to the Office for Human Research Projects (OHRP). All IRB inactivated studies using investigational drugs or devices will also be reported to the Food and Drug Administration (FDA).
If the study is completed, a researcher must complete a shorter close-out version of the continuing review form as a "final report" on the project.
Continuing review requires that you complete the Continuing Review Form, attach a current consent form. The Continuing Review Form requires the following information:
Incomplete forms will be returned, which may cause a delay in getting the study on the appropriate committee agenda.
A project usually merits the same level of review in continuing review as it received originally expedited or full committee review.
Once the IRB has approved a project, it must be carried out as planned. Any changes in subject population, recruitment plans, research procedures, study instruments, study sites, or major research personnel must be prospectively approved by the IRB. Enacted changes without prior approval consititute protocol violations.
Researchers planning a change should:
If a principal investigator is on sabbatical leave from the University, an interim PI must be appointed. The IRB should be informed of this person's qualifications and the new PI should write to the IRB accepting the responsibility for the treatment of subjects. If a researcher leaves the University permanently, the IRB should be notified both of any interim investigators and of the final replacement or the study will be filed as "inactive".
Some minor changes are handled by administrative action. Many changes receive expedited IRB review. Changes that affect the risk/benefit ratio may require full review. Implementation of the change must wait for the IRB's approval.
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO)
Federal regulations [45CFR46.103(b)(5) and 21CFR56.108(b)(1)] require the IRB to ensure that investigators promptly report “any unanticipated problems involving risk to subjects or others” (UPIRTSO). The IRB defines UPIRTSO as any problem or event which in the opinion of the local investigator was unanticipated, reflects new or increased risk to the subjects and was possibly related to the research procedures. The IRB makes the determination of whether the unanticipated problem meets the criteria as a UPIRTSO.
What to Report
The following events meet the IRB’s definition of UPIRTSO and should be reported within the 10 day time frame:
Note that issues such as whether the event was on-site or off-site or whether the event involved a death are no longer of primary relevance in determining what should be reported. If the event meets all 3 criteria in the IRB’s definition of UPIRTSO, it should be reported using the reporting form within the 10-day time frame.
Unanticipated (unexpected) problems/events are those that are not already described as potential risks in the consent form, not listed in the Investigator’s Brochure or not part of an underlying disease.
Anticipated (expected) problems are those that are already described as potential risks in the consent form, listed in the Investigator’s Brochure or part of an underlying disease. These do NOT meet the IRB’s definition of UPIRTSO and should be reported in summary form only at the time of IRB continuing review. For example, if death is an expected outcome, this event should be reported only at the time of continuing review.
Problems/events that are unanticipated should be reported to the IRB within 10 working days only if in the opinion of the local investigator they are possibly, probably or definitely related to the research procedures. Unanticipated problems/events that the local investigator deems unlikely or not related do NOT meet the IRB’s definition of UPIRTSO.
Reviwing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events dated January 15, 2007 can be found at the Office for Human Research Protections (OHRP) Website.
Once received in the IRB office, completed UPIRTSO reporting forms will be pre-reviewed by IRB staff to determine the level of IRB review required.
All problems/events that do NOT meet the IRB’s definition of UPIRTSO should be reported to the IRB in summary form (using a table or spreadsheet) at the time of continuing review. Accompanying documentation (sponsor report forms, etc.) should NOT be included with this summary. If received, such accompanying documentation will be returned to the investigator.
As a study progresses and the risks and benefits of participating in the study are better understood, researchers sometimes find that the study must be stopped. For example, in some placebo-controlled trials, preliminary findings may give compelling evidence that a new treatment is efficacious. It then becomes unethical to continue giving placebos. (This occurs most frequently in multicenter trials in which a central statistical center receives and processes large volumes of data from several sites.)
In such cases, the investigator should write to the IRB, describe the findings and the need to suspend the placebo portion of the study. If the IRB agrees, the researcher should identify all subjects who received a placebo and invite those subjects to continue in an "open label" study in which all subjects receive the study medication.
Researchers should maintain a file of all documents concerning the use of human subjects in research for 3 years from completion of IRB related work and 6 years for HIPAA, including original paperwork whenever possible, and a copy of everything else. The principal investigator's records should be a mirror image of the IRB's records: where the IRB holds an original, the principal investigator should hold a copy, and vice versa.
The documents that researchers should have on file include:
Original signed consent forms should be kept in a secure location separate from correspondence with the IRB but readily available to inspectors. Whenever a subject is a patient of the Fairview Health Services, a copy of the signed form should be placed in the patient's medical chart as a precautionary measure, in case complications with the research protocol occur and emergency medical treatment is required.
IRB records are subject to inspection by federal authorities. Sanctions for incomplete or nonexistent records include suspension of funding, fines, exclusion from future funding, and suspension of laboratory access.
You will need Adobe Acrobat installed on your computer to view and print PDF files.