Clinical trials require ongoing and continuous monitoring of the safety for study participants. According to 21 CFR 312.64, Investigators are required to “immediately report to the sponsor any serious adverse event (SAE), whether or not considered drug related, including those listed in the protocol or investigator brochure and must include an assessment of whether or not there is a reasonable possibility that the drug caused the event.”
For industry sponsored clinical trials, investigators are typically required to report any SAE to sponsor with 24 to 48 hours of becoming aware of an SAE. The recipients of the SAE are typically the pharmacovigilence (PV) group or drug safety group who are independent of the clinical research team and are dedicated for receiving (from the investigational sites), clarification (with the investigational sites), analyzing, and reporting of SAE information. The transmittal of SAE from investigational sites to sponsor is typically through faxing or emailing the paper SAE form which is separated from the adverse event (AE) case report form used in clinical and data management group. Investigators will need to enter the duplicate information for SAE into the case report form (used by the clinical and data management group) and into SAE form (used by the PV or drug safety group). Since the SAE information at clinical database and the drug safety database may have discrepancies, the SAE reconciliation is required to make sure the consistency between the clinical database and the drug safety database.
With more and more clinical trials conducted using electronic data capture (EDC) to collect the data, it is natural to think about the transition of SAE data collection for PV or drug safety group through EDC system instead of faxing and emailing the paper SAE forms. By using EDC system to collect the SAE information, investigators will only need to enter the SAE data one time at one system (EDC). Once SAE information is entered into EDC, an alert will be sent to the designated group. This process will avoid the potential data discrepancies between clinical database and drug safety database and will avoid the necessity of the SAE reconciliation.
One concern about this process is that SAE form typically collects more items than AE form. Additional information for SAE is required per ICH guidance E2B “MAINTENANCE OF THE ICH GUIDELINE ON CLINICAL SAFETY DATA MANAGEMENT : DATA ELEMENTS FOR TRANSMISSION OF INDIVIDUAL CASE SAFETY REPORTS”
This concern can easily be addressed by adding these additional fields required for SAE reporting to the AE case report form in EDC database.
CDISC/CDASH has just published anaddendum to AE collection for serious events. The addendum specifically addressed the concern for collecting SAE through EDC system (instead of paper).
The page 4 of the CDASH SAE addendum says:
“Electronic data capture (EDC) is recognized as an efficient and time saving method for capturing clinical data. EDC also offers a more efficient process for SAE information capture than the traditional paper form; sponsors can use information already available in the Clinical Data Management System (CDMS) to populate the same data elements on an SAE report form. Typically, such data are housed in a clinical study database. All SAE data that are not extracted from the clinical study database are typically housed in a separate safety database. The relationship between drug safety data and clinical trial data that commonly manifests in two distinct data acquisition processes can be enhanced by minimizing duplicative data collection and easing the safety data reconciliation processes.
Clinical Data Acquisition Standards Harmonization (CDASH) is the standard applied to clinical data at point of capture (http://www.cdisc.org/cdash). CDASH contains an Adverse Event domain intended for capture of adverse event information in the CDMS (the AE CRF).
The draft CDASH Adverse Event Addendum to CDASH version 1.1 expands the current Adverse Event (AE) domain to include data elements for the capture of serious adverse event information in an SAE Form and, when indicated, will also allow for the generation of an E2B message for reporting an Individual Case Safety Report (ICSR) to Health Authorities. The content of an ICSR is specified by the International Conference on Harmonization (ICH) in the Guideline on Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (E2B R2). “
- Unifying Drug Safety and Clinical Databases
- SAE Reporting In EDC Trials
- Safety Reporting From Clinical Trials—What Regulators Expect