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). “
Further
Reading
- Unifying Drug Safety and Clinical Databases
- SAE Reporting In EDC Trials
- Safety Reporting From Clinical Trials—What Regulators Expect
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