The assessment of severity (or grade) and causality (or relationship to the study product) for adverse events should be conducted by the PI (i.e., Clinical Investigator) listed on the Statement of Investigator, Form FDA 1572. It can also be delegated to a qualified sub-investigator listed on Form FDA 1572. Serious adverse events (SAEs) must be reported to DMID-CROMS PVG and reviewed by the PI or qualified designee listed on the Form FDA 1572 and delegation of authority (DOA) log.

DMID uses a standard SAE form for all DMID sponsored/supported studies. DMID SAE forms submitted to DMID-CROMS PVG are considered source documents. If the study would like to use a different SAE form, the form must be reviewed and approved by DMID.
Depending on the study, AEs are entered on case report forms (CRFs). CRFs are entered either electronically or paper based. Generally, CRFs are not source documents. If the AE CRF must be used as a source document, please contact DMID for additional guidance.

Monitors cross-check submitted AEs/SAEs against the source documents. The PI or qualified designee should initial or sign the source document or CRF. For electronical data systems, monitors use the unique identifier (electronic signature) to determine who entered or approved the submission. If an electronic signature is not available, the document should be printed and signed or initialed.

If there are several AEs or clinical signs and symptoms that are relevant and temporal to the SAE diagnosis, the AEs can be grouped together to support a diagnosis (e.g., low hemoglobin, dyspnea, pallor = anemia). The diagnosis (not the procedure or treatment) should be reported as the SAE term. Additional AEs or clinical signs and symptoms can be described in the narrative section of the SAE form.

If the AE is not relevant to the SAE, the AE should be listed separately on the AE CRF.

Yes. However, each protocol or associated manual of procedure will determine how these should be collected and reported. Please contact DMID for additional guidance, if needed.

A Serious Adverse Event is an event that meets one or more of the following criteria:

• Results in death
• Is immediate​ly life threatening
• Requires inpatient hospitalization or prolongation of existing hospitalization
• Results in persistent or significant disability/incapacity
• Is a congenital anomaly/birth defect​
  
• Is an important medical event ​
• Requires intervention to prevent permanent impairment or damage

AESI is an adverse event (serious or non-serious) that is of scientific and medical concern specific to the study product or research program (e.g., myocarditis for mRNA vaccines). Therefore, ongoing monitoring and rapid communication by the Investigator to the sponsor may be appropriate and such an event may require further investigation in order to characterize and understand it.

The protocol will define AESIs that are reported to DMID-CROMS PVG. AESIs are reported to DMID-CROMS PVG using the DMID SAE Form.​

When reporting an AESI to DMID-CROMS PVG, Investigators are instructed to select “AESI (Adverse Event of Special Interest)” on section 2 of the DMID SAE Form.

• Medically-Attended Adverse Events (MAAEs) – defined as AEs with medically attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events (e.g., abnormal vitals) identified at a routine study visit will not be considered MAAEs.
• New-Onset Chronic Medical Conditions (NOCMCs) – defined as any new International Classification of Diseases diagnosis (per current International Statistical Classification of Diseases and Related Health Problems) that is applied to the participant during the course of the trial, after receipt of the study product, that is expected to continue for at least 3 months and requires continued health care intervention.
• Potentially Immune-Mediated Medical Conditions (PIMMCs) – defined as a subset of adverse events that include autoimmune diseases and other inflammatory or neurological disorders of interest that might have an autoimmune etiology.
• Sponsor requested adverse events – defined as an adverse event that would not otherwise be reported to DMID-CROMS PVG, but requested to be submitted to DMID-CROMS PVG by the sponsor.

Wh​en reporting other reporting requirements to DMID-CROMS PVG, Investigators are instructed to make the appropriate selection on section 2 of the DMID SAE form.

The protocol provides Investigators with instructions on protocol-required reporting of safety events and how to report to DMID-CROMS PVG. All safety events that are required to be reported to DMID-CROMS PVG should be sent via the electronic reporting system (when available); via email at PVG@dmidcroms.com ; or via fax at 1-800-275-7619 (US) or 1-301-897-1710 (Outside US).

The DMID SAE Form for the reporting to DMID-CROMS PVG can be accessed here: SAE Form v 4.0

In order for DMID-CROMS PVG to process a case submitted by an Investigator, the following information must be included on the SAE Form:

• Reporter identification
• Protocol number or title
• Subject identifier
• Adverse event term
• Reporting criteria or seriousness criteria
• Causality assessment
• Event outcome
• Study product information

Additional reporting guidelines can be found here: SAE Form Guidelines v 4.0

Sites can send redacted medical records that are relevant for their submitted adverse event to DMID-CROMS PVG. Investigators must redact any personal identifying information such as names, dates of birth, and addresses from source documents prior to sending. Investigators are requested to include the participant ID or case number (if known).

DMID-CROMS PVG will send various queries to the sites for resolution. These include queries to clarify reported safety event details, information that is discrepant between the safety and clinical databases, and information missing from the SAE form. DMID-CROMS PVG may also send queries received from pharmaceutical companies, when applicable.

Investigators should submit a follow-up SAE Form or follow DMID-CROMS PVG instructions described in the query. For some clarifications or minor queries, the Investigator may respond to DMID-CROMS PVG’s email or submit additional information as requested via email to PVG@dmidcroms.com or fax at 1-800-275-7619 (US) or 1-301-897-1710 (Outside US).​​​​​​​​​​​​​​​​​​​