Serious Adverse Event Reconciliation - Aditi Bhat

Agenda Adverse Event Serious Adverse Event (SAE) Collection of SAE’s SAE Reconciliation and Reasons for performing reconciliation Different databases Paper studies and Electronic studies Points/Fields to be reconciled Points to remember before performing SAE reconciliation Reconciliation Process Discrepancy with solutions Query process Roles and Responsibility Data base lock activity Documents

Adverse Event An adverse event is any unfavourable and unintended sign (including abnormal laboratory findings), symptoms or disease temporarily associated with the use of a medical (investigational) product, whether or not related to the medical (investigational) product.

Serious Adverse Event SAE (Serious Adverse Event) : Any untoward medical occurrence that at any dose results in:- Death Is life threatening Requires inpatient hospitalization or prolongation of existing hospitalization Persistent or significant disability/incapacity Congenital anomaly or birth defect Requires intervention to prevent impairment or damage

Collection of SAE’s When SAE is reported on the site, it has to be reported to the Sponsor within 24 hours and to regulatory authorities within 7 days. If the Site does not adhere to the mentioned timelines, it will be considered as protocol deviation.

SAE Reconciliation and reasons for performing reconciliation It is necessary because SAE data is considered as CRITICAL DATA in both the safety and the project database. Clinical database is made up of dosing, demography, adverse event and final subject summary pages; all of which are data points that make up the case that are reported to the safety database. It is essential to understand that these data is submitted to Regulatory Agencies at the end of the study and for subsequent aggregate reporting which occurs well after database lock.

Different databases used to perform reconciliation Safety database: Sapphire BOR, Argus, etc. (Mainly built for Pharmacovigilance purpose) Clinical database: AMOS, RAVE, COOL, INFORM, ORACLE

Paper studies Electronic studies Data is entered on Paper case Report Form Data entry associates will enter the data manually in Clinical database Example: AMOS Data is captured in electronic case report Form Investigator enters data in to database Examples: RAVE, INFORM

Fields to be reconciled Site Number Subject Number Randomization Number AE Term reported (verbatim Term) Preferred term (Coded Term) Start date of the event Stop date of the event Investigational drug Causality Outcome Seriousness criteria AE became SAE date

Points to remember before performing reconciliation Reading of Data Handling Plan and Protocol are MUST before starting the reconciliation of the study which will give the below details, When to start SAE reconciliation considering First Patient First Visit Which fields to be reconciled What would be the cutoff date for SAE Which SAEs to be considered as expected SAEs, Unexpected SAEs, Which SAEs to be considered as End points. End points are to be captured or not Details of CRA, Investigator, CTH Frequency of reconciliation to be performed

Process of reconciliation Team Lead will assign the study Apply for the required access Read Protocol and DHP Post getting the access send mail to study team to discuss the reconciliation date for the particular study Pull the safety listings from Safety database / request for the Safety listings And pull the Clinical listings by SAS or the available tool Perform the reconciliation Record the discrepancies and action to be taken in one sheet [generally called as SAE reconciliation Spread Sheet (SRS)] Raising queries - For missing SAEs query should be raised within 24 hours of the reconciliation Before raising a query, kindly check if the query has been raised by TDM/DM for the particular SAE

Discrepancies with resolutions

Query Process For missing SAEs from either of the database, query to be raised within 24 hours of the reconciliation process If Query is not getting answered in 48 hours for missing SAE, send mail to CRA keeping CTH and study team in loop For other discrepancies turn over time is 7 working days Before raising any query, please check if the query has been raised Every week Open query report to be run and if answers of raised queries are satisfactory in nature, query can be closed. If not a re-query can be raised After raising 3 re-queries, answer is not satisfactory; send mail to CRA keeping study team in a loop

Roles and Responsibility SAE Reconciler: Extracting the data from Clinical database and Safety database Reconciliation mandatory/agreed upon SAE data points Communicating with coders to resolve the coding issue Checking internally with data entry to resolve data entry issues if the study is paper based Raising queries in the database Preparing SRS log for discrepancies observed and action taken Filling the monthly ongoing reconciliation form Filling the Final SAE Reconciliation form.

Database lock activity SAE Reconciler will receive a mail regarding database lock from study team. He/she needs to confirm about cutoff date regarding SAE Frequency of reconciliation will be discussed with the study team. Query report to be pulled on a regular basis If queries are not getting resolved, mail can be sent to CRA keeping study team in a loop Discrepancy report can be sent to the study team Patient safety to be reported for the database lock.

Documents SAE Reconciliation Spreadsheet Monthly Ongoing SAE Reconciliation Form Safety Database update Request Form Coding Mismatch Tracker Final SAE Reconciliation Form

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