Changes to Eliminate Immediate Hazards to Subjects Guidance

Changes to eliminate an apparent immediate hazard to subjects

Changes in approved research initiated without prior IRB review and approval are allowed under both the Common Rule and FDA regulations ONLY to eliminate apparent immediate hazards to subjects.  These changes are expected to be rare.  Any such changes made must be reported to the IRB within fourteen (14) business days of implementation as both an unanticipated problem and a change of protocol.

• In the unanticipated problem report, the investigator must give an overview of the situation including what changes were implemented prior to IRB approval and why these changes needed implementation prior to IRB approval to prevent immediate hazard to study subjects.
• In the change of protocol, the investigator needs to specifically explain any changes to the protocol and study documents (e.g., informed consent documents) that are required.

The IRB then will review the unanticipated problem report to determine if the action taken by the investigator was necessary to eliminate an apparent immediate hazard to the subject(s). The Change of Protocol will be reviewed to determine if the changes implemented are consistent with ensuring the subject's continued welfare.

If a change of protocol is implemented prior to IRB approval and the IRB determines that the change was not necessary to eliminate apparent immediate hazards to a subject, the investigator’s action may be considered to represent noncompliance with the regulations governing human subjects research and result in additional action by the IRB.

Other Changes Needed for Subject Safety Reasons That Do Not Present an Apparent Immediate Hazard to Subjects

Study sponsors may require changes in study procedures in response to new safety information. In many cases, however, the changes are not required to eliminate an apparent immediate hazard to subjects. Prior IRB review and approval of these types of changes is required before any changes in study procedures can be implemented. Investigators who think a change to study procedures must be made as soon as possible to address subject safety issues should contact the Health Sciences IRBs office for guidance before making any changes without IRB approval.