Submission of IND Safety Reports
In January 2009 the FDA released the following information in a guidance document for clinical investigators, sponsors and IRBs in reference to Adverse Event Reporting:
- Investigators are required to report promptly “to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug. If the adverse effect is alarming, the investigator shall report the adverse effect immediately” (21CFR 312.64(b)).
- Sponsors are specifically required to notify all participating investigators (and FDA) in a written IND safety report of “any adverse experience associated with the use of the drug that is both serious and unexpected” and “any finding from tests in laboratory animals that suggests a significant risk for human subjects” (21CFR312.32(c)(1)(i)(A),(B)). And, more generally, sponsors are required to “keep each participating investigator informed of new observations discovered by or reported to the sponsor on the drug, particularly with respect to adverse effects and safe use” (21CFR312.55(b)).
- Investigators are required to report promptly “to the IRB all unanticipated problems involving risks to human subjects or others,” including adverse events that should be considered unanticipated problems (21CFR56.108(b)(1); 21CFR312.53(c)(1)(vii); and 21CFR312.66).
The increased use of multi-center studies and international trials has complicated the reporting pathways for adverse event information described in the regulations. In particular, the practice of local investigators reporting individual, unanalyzed events to IRBs, including reports of events from other study sites that the investigator receives from the sponsor of a multi-center study—often with limited information and no explanation of how the event represents an unanticipated problem—has led to the submission of large numbers of reports to IRBs that are uninformative. Many IRBs have expressed concern that the way in which investigators and sponsors of IND studies typically interpret the regulatory requirement to inform IRBs of all "unanticipated problems" does not yield information about adverse events that is useful to IRBs and thus hinders their ability to ensure the protection of human subjects.
LSUHSC-S Reporting Policy:
The IRB is required by the FDA and DHHS to review “unanticipated problems involving risks to participants or others.” IND safety reports do not necessarily meet the definition of an unanticipated problem. Often, however, sponsors send IND safety reports to investigators and instruct the investigators to submit them to the IRB.
Additionally, federal regulations require a sponsor, not a study investigator, to submit IND safety reports to the FDA and to participating investigators.
The LSUHSC-S IRB has established different reporting requirements for those adverse events that should be considered unanticipated problems from those that are not. This change in reporting requirements is to make the adverse events information the IRB receives more informative and useful.
When must a LSUHSC-S Investigator submit IND safety reports to the IRB?
The investigator must submit IND safety reports to the IRB only in the following cases:
(1) When the report meets the definition of an unanticipated problem (LSUHSC-S HRPP
Policy Section 8.2), or
(2) When an IND safety report triggers a sponsor-required change in the research
protocol or consent form, or
(3) when the sponsor indicates the safety information must be reviewed by the IRB to
determine that either a change in research is required or currently enrolled subjects
should be informed of the new information.
Is an Investigator required to review IND Safety Reports?
Yes. Investigators should review all IND safety reports sent by the sponsor.
- If the report meets (1) the definition of an unanticipated problem, the PI must submit an Unanticipated Problems and Other Events Requiring Prompt Reporting Form and include a copy of the IND safety report.
- If the report meets item (2) or item (3) above, the PI must submit a Modification Request Form and include a copy of the IND safety report.
- If the IND safety report does not represent an unanticipated problem or does not contain information that requires a change in protocol or consent form, the report does not have to be submitted. It should be kept by the investigator with the other regulatory documents provided by the sponsor
If a sponsor requires submission of all IND safety reports to the IRB, how should they be submitted?
If a sponsor requires submission of all IND safety reports to the IRB, for paper based studies use the IND Safety Report Summary Form to list all of the IND safety reports that do not trigger a change in research. A copy of the IND Safety Reports should be attached. The LSUHSC-S IRB staff will acknowledge that the form and accompanying reports were received.
The IND safety reports will be acknowledged but will not be reviewed by the IRB. The acknowledgement is not confirmation of IRB review and approval of the IND safety reports.
Investigators are not required to submit IND safety reports received after a study has been terminated or closed.