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Reconciliation of the Serious Adverse Event

Serious Adverse Event data Reconciliation is the comparison of key safety data between two data bases. (Clinical data base defined as a closed data base and a safety data base defined as an open data base.

Clinical data base defined as a closed since it can receive data only for a very short period of time. A safety data base defined as an open data base since it continues receive new SAE’s or updates of pre-existing SAE’s.

SAE Reconciliation is done to assure consistency

  • Between the two bases for the numerosity of SAE recorded for the same clinical trial
  • Among the key safety data defined in DMP/SOP

SAE Reconciliation occurs several times during the whole study period and it depends on

  • the frequency of data received
  • the scheduling of safety updates and the timing of interim and final reports from Pharmacovigilance to regulatory authorities on serious adverse event findings.

The capture of SAEs in both the clinical trials database and the safety database should be standardized with regard to data captured and coding of terms (e.g., event description, start and stop date, relation to study drug, verbatim term coding, etc.).

All information (data and metadata elements) to be reconciled during this procedure shall be identified and documented in the study plan before the first patient is enrolled in the clinical research protocol.

Key safety data:

When comparing the key safety data it is necessary that

key safety data values are same (both in manual and electronic form)

they are in same format(electronic comparison)

they share the same values code list for the  same field when applicable(both in manual and electronic comparison)

Procedure:

Before starting with SAE Reconciliation the DM department should ensure that all data to be included  in the process have been entered , coded and validated with no dcf pending  , data must be final for that/ those patient(s) at the time of Reconciliation.

The procedure organized as it follows:

  1. retrieving data from the two data base:

First step is to retrieve the data from the data base and to create two hard copy listing/two electronic listings and two sources will be reconciled through direct comparison by adding each difference this step can be done by DM department when receiving data from Pharmacovigilance department or vice versa.

  1. Check between information

Checks to be done by DM before starting comparing the key safety data:

  • Verify that number of patients that experienced SAE’s in both the data bases is the same at the time of reconciliation.
  • Verify that all SAE’s recorded in the safety data bases are recorded in the clinical data base as well and vice versa at the time of reconciliation.
  • Verify all the key safety data defined as mandatory in the DMP.
  1. Actions to be taken
  • SAE’s that are in the clinical data base but not in safety data base

Those can be potentially unreported events, so copies of the appropriate CRF pages must be forwarded to Pharmacovigilance.

  • SAE’s that are in safety data base but not in clinical data base

The DM has no right to add new SAE without any data clarification form signed by the Investigator. No SAE’s can be added to the clinical data base without been monitored against the source documents.

Actions taken on key data base discrepancies (acceptable)

If difference in the key data value then depending on the nature of discrepancy the DM will decide to issue data clarification form to the site or to accept those discrepancies since defined as acceptable in the DMP and so there is no need to query the investigator.

Actions taken on key data base discrepancies (unacceptable)

The review of all unacceptable discrepancies is made by comparing the information reported in the clinical database and SAE form that is attached to a CRF

Before issuing the DCF an agreement with the Pharmacovigilance department is taken since the nature of DCF can change SAE from non-expedited to expedited.

  1. Process tracking

All the necessary actions will be taken by the two departments to solve the corresponding discrepancies and the forms will be signed for the approval from the concerned.

Changes to either database, as a result of reconciliation activities, will be made in a timely manner to expedite clinical study closure activities and/or safety reporting requirements.

Local QA formally conducts a review of the reconciliation results for accuracy

When using a paper CRF the pages are entered by data entry operators. Best practice is for a first pass data entry to be completed followed by a second pass or verification step by an independent operator. Any discrepancies between the first and second pass may be resolved such that the data entered is a true reflection of that recorded on the CRF. Where the operator is unable to read the entry the clinical data manager should be notified so that the entry may be clarified with the person who completed the CRF.

When an electronic CRF is in use data entry is carried out at the investigative site where the clinical trial is conducted by site staff

The CRF collects Adverse Events reported during the conduct of the clinical trial however there is a separate process which ensures that Serious Adverse Events are reported quickly. The clinical data manager must ensure that data is reconciled between these processes.

Data validation

Data validation is the process of testing the validity of data in accordance with the protocol specifications. Edit check programs are written to identify the discrepancies in the entered data, which are embedded in the database, to ensure data validity. These programs are written according to the logic condition mentioned in the DVP. These edit check programs are initially tested with dummy data containing discrepancies. Discrepancy is defined as a data point that fails to pass a validation check. Discrepancy may be due to inconsistent data, missing data, range checks, and deviations from the protocol. In e-CRF based studies, data validation process will be run frequently for identifying discrepancies. These discrepancies will be resolved by investigators after logging into the system. Ongoing quality control of data processing is undertaken at regular intervals during the course of CDM. For example, if the inclusion criteria specify that the age of the patient should be between 18 and 65 years (both inclusive), an edit program will be written for two conditions viz. age <18 and >65. If for any patient, the condition becomes TRUE, a discrepancy will be generated. These discrepancies will be highlighted in the system and Data Clarification Forms (DCFs) can be generated. DCFs are documents containing queries pertaining to the discrepancies identified.

Role Responsibilities
Study Coordinator
  • Work with the Drug Safety Officer and the Clinical Research Study Team to reconcile SAEs captured in the clinical data management application with SAEs captured and recorded in the Safety Database.
  • Make the necessary changes and/or updates to the clinical data management application.
Drug Safety Officer
  • Assist in reconciling SAEs in line with this SOP
  • Make the necessary changes and/or updates to the Safety

Database.

Clinical Study Team
  • Provide the necessary clinical information or interpretation input on SAEs captured during the conduct of the clinical research trial, including input on coding of events
Local QA
  • Conduct a formal review of the reconciliation processes and performs a quality check on updates to the databases.

Overview of the process

Two departments are involved

Drug Safety and Pharmacovigilance

Clinical Data Science – Data Management section

SAE data is collected in Safety Database

Via SAE Report Form and data entry

Data validation

100% check of entered items

Medical review

Medical evaluation

MedDRA coding of event

Finalization

Ask for follow-up information

Lock case and report to authorities within 7 days (fatal and life-threatening) or 15 days (for related non-fatal SUSARs – Serious unexpected suspected adverse drug reactions)

SAE Reconciliation is performed by Data Management (with support of DSP)

For this we need a SAE Reconciliation Plan

Process is embedded in DM SOP

Create Data Management Plan

Working Practice Document

DMP Module 2: Enter and validate study data

SAE Reconciliation process is described

Appendix 4

List of items to be reconciled

For each study a DMP Module 2 will be created and signed off by Data Manager, Study Manager and Pharmacovigilance Physician

The SAE Reconciliation process can start

The data in the Clinical and Safety databases are available

We have an approved SAE Reconciliation Plan