Regulatory requirements, including the Food and Drug Administration (FDA) regulations, International Conference on Harmonisation (ICH) Guidelines for Good Clinical Practice (GCP), and European Union (EU) Clinical Trials Directive, set forth safety monitoring and reporting responsibilities of sponsors and investigators to ensure the safety and protection of human subjects participating in clinical trials.
The NIAID Division of Microbiology and Infectious Diseases (DMID) relies on investigative sites to provide accurate and thorough initial assessments of adverse events and follow-up secondary to initial reports of these events. DMID has centralized safety reporting through its Clinical Research Operations Management contract. Criteria and reporting procedures are detailed in the clinical protocol. For IND/IDE studies all reporting must comply with 21 CFR 312.32 and 812.150 respectively. Studies conducted outside of the United States must also comply with any local regulations.
Serious Adverse Event (SAE) Reporting
The FDA definition states: An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the investigator or sponsor, it results in any of the following outcomes:
- A life-threatening adverse event*
- Inpatient hospitalization or prolongation of existing hospitalization
- A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or
- A congenital anomaly/birth defect
- Important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.
* Life-threatening adverse event. An adverse event is considered “life-threatening” if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not include an adverse event, had it occurred in a more severe form, might have caused death.
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 24 hours of site awareness) on a DMID SAE form, or otherwise agreed upon SAE form, to the DMID Pharmacovigilance contractor at the following address:
DMID Pharmacovigilance Group
Clinical Research Operations Management Support (CROMS)
6500 Rock Spring Dr., Suite 650
Bethesda, MD 20817, USA
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US)
SAE FAX Phone Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US)
SAE Email Address: PVG@dmidcroms.com
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance contractor and should be provided as soon as possible. The DMID Pharmacovigilance contractor will notify the DMID medical monitor and clinical protocol manager.
- Role of Medical Monitors
- Unblinding Individual Participants in DMID Clinical Research
- Responsibility for Response to Food and Drug Administration Inspections of DMID-Sponsored Research
SAE Forms and Guidelines
The below is provided as an example. Each protocol should adapt a relevant toxicity table appropriate to the study.
- Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)
- Selected References page for
- Food and Drug heading- Investigational New Drug regulations 312.32 and 812.150
- International Congress on Harmonisation heading for Good Clinical Practices (GCP) E6 and Clinical Safety E1-2F
- Safety Reporting -Guidance for Industry and Investigators - Safety Reporting Requirements for INDs and BA/BE Studies
- Protocol and Consent page for protocol templates
- Training Opportunities page for self-guided training on adverse event and serious adverse events identification and reporting.