Initial Review

IRB review can be conducted by the full IRB committee or by a single delegated person for an expedited review. Any research that is determined to be more than minimal risk must be reviewed by the full committee. If the research is no more than minimal risk, then the IRB can allow an expedited review, though the IRB may always choose to convene the full board even for minimal risk projects. Either the full committee or the expedited reviewer has the authority to approve the protocol, require modifications (to secure approval), or disapprove the protocol.

The review of the protocol includes, for example, confirming that risks are minimized; that the risks are reasonable in relation to the potential benefits of the knowledge expected to be produced; that subject selection is equitable; whether informed consent or a waiver or alteration of informed consent is appropriate; if informed consent is required, the content of the informed consent form; privacy and confidentiality issues; and whether there are potentially vulnerable subjects that may require additional protections.

Of note, the Common Rule (45 CFR §46) has 3 subparts that require additional protections for specific populations. The IRB will include these requirements in their review as appropriate. The 3 subparts include pregnant women and fetuses, research with prisoners, and research with children.

The IRB also considers institutional issues that may have an impact on the research. The specifics of individual protocols may trigger ancillary committee reviews, such as pharmacy, radiation safety, biomedical engineering, or nursing. The numbers and types of ancillary committees vary by institution. In addition, the IRB must review the adequacy of resources to complete the study, the competency of the study team, conflict of interest issues, and any institutional policies or local laws and regulations that are relevant to the research.

Once the Protocol Is Approved

The IRB continues to play a role during the life of the protocol, as described below.

Continuing Review

Once a protocol is approved, continuing review, usually on an annual basis, may be required. This is a formal review of the study with focus on enrollment, adverse events, unanticipated problems, protocol deviations, and any other challenges encountered. Generally, continuing review is only required for protocols that were initially reviewed by the full committee and that continue to enroll participants. As with initial review, the IRB has the authority to approve, require modifications (to secure approval), or disapprove the continuing review submission. The IRB will notify the investigator of the need, or not, for the protocol to undergo continuing review.

Amendments

When a protocol is approved, the expectation is that the research will be conducted in compliance with the protocol as written. If changes are required or desired, these changes must be prospectively reviewed and approved by the IRB. Except for urgent actions required for subject safety, no change in research conduct should be made without prior IRB approval. If the amendment includes changes to the informed consent form, the IRB may require reconsent of subjects already enrolled and active in the study.

Unanticipated Problems and Adverse Events Involving Risk to Subjects or Others

IRBs require the reporting of unanticipated problems, defined as unexpected events (by nature, severity, or frequency) related or possibly related to the research and posing increased risk of harm to subjects or others. Adverse events are closely related to and may overlap with unanticipated problems. Adverse events are evaluated as expected or unexpected, serious or nonserious, and related or unrelated to the research. The highest level of concern is for serious, unexpected, and related adverse events. Investigators are encouraged to work with their IRB to determine which events to report and the urgency of reporting. Many institutions require any unanticipated problem resulting in death to be reported as soon as possible and no later than 3 calendar days after the event. Seven or 10 days is often required for the reporting of other unanticipated problems. The reason for reporting is to allow the IRB to consider if a change to the protocol or the consent form is merited or if approval of the study should be suspended.

Protocol Deviations

As noted previously, research must be conducted as specified in the approved protocol. If there are deviations from the approved protocol, reporting to the IRB is required. Some institutions differentiate between protocol deviations and protocol violations. A deviation is an event that does not have a significant effect on subjects or the research (such as a late follow-up visit). A violation is an event that does have a significant effect on subjects or the research (such as enrolling individuals who do not meet critical eligibility criteria). In some cases, deviations or violations may be unanticipated problems, and some may trigger the need for an amendment. Investigators should work with their IRB to determine when deviations should be reported.

Termination of the Protocol

The IRB has the authority to terminate a protocol if the study is not being conducted as approved or if serious harms have arisen related to the research.

Availability to Respond to Participant Questions and Concerns

The IRB requires that the informed consent form include a list of persons to contact for answers to pertinent questions about the research. While the IRB is often the contact for questions relating to research subjects' rights, the principal investigator should identify a contact for questions regarding the research activities and or any research-related injury. In some situations of high-risk interventional research, this may require 24-hour coverage.

Observe Informed Consent Process

The IRB has the authority to observe the consent process to ensure that all required elements of consent are being discussed and that the process is free from coercion and undue influence.