VI.Add I.4. Management of duplicates cases

Duplicate cases are generally managed through a process of merging two or more cases into one master case.

This process can consist of one of the following approaches:

• The master case can either be based on one of the existing cases, with information from the other subordinate duplicate cases added unless the same, or more precise, information is already present in the master case (this is referred to in this document as “Allocation of a master case”), or;
• The master case can be created as a new case combining the information from the subordinate duplicate cases (this is referred to in this document as “Creation of a master case”).

Regardless of the approach chosen, the master case should always contain all case reference numbers from all subordinate duplicate cases, such that they can be easily traced. The master case should reflect the most accurate and up-to-date information available to the organisation.

Both concepts are acceptable; however, whatever method chosen, the process should be welldocumented. Proper record management should ensure that all received ICSRs for all individual cases can be tracked adequately, including all information as reported by the primary sources, the reporters and the report senders. The ‘Date report was first received from source’ 9 and ‘Date of receipt of the most recent information for this report’10 of the duplicates must remain unchanged unless new information is received.

A challenge to be faced in duplicate management relates to situations where conflicting or divergent information is provided by different senders. Attempts should be made to obtain clarification. If this is not possible, the case narrative should reflect information from both sources.

The master case should be a complete representation of the case, whereby all information should be presented in full compliance with ICH-E2B and the guidance provided in GVP Module VI. Regarding the adverse reactions, one can choose to merge all reported reactions as presented in the duplicated cases in the master case. However, if the reactions reflect similar concepts, but one is more specific (e.g. ‘liver injury’ versus ‘fulminant hepatitis’), one may choose the more specific term. Medical judgement should always be applied in these and other decisions which are based on whether the extra specificity is clinically important. If there is conflicting information, it is not considered appropriate to reflect this twice in the structured fields of the master case as this would impede calculation of cumulative doses. Since the completeness of the cases can vary (e.g. one case may have follow-up information clarifying and amending certain points, whereas the other simply has the initial information), the most accurate information should always be used.

It may, however, not be possible to determine which case is the most accurate and complete, and so in some cases, where it is necessary and possible and where a field has been populated differently in the duplicate cases, either one value or another may be chosen, or an average be stated, with clear reference in the case narrative that there is conflicting information obtained from different sources and what the conflicting information is. It will not always be appropriate to do this, especially in cases of suspected overdose or underdose, and medical judgement is always required in such cases.

If information has been populated in one case, but not in another, and there is no reason to believe that the lack of such information is necessarily correct, then it is appropriate to add the extra information, e.g. case 1 has no concomitant medication, whereas case 2 has paracetamol as concomitant medication; unless case 2 is the more recent case, and clearly states that the patient was not, contrary to previous information, receiving paracetamol, then the paracetamol should be included as concomitant medication in the master case.

VI. Add I.4.1. Process of managing duplicates detected during periodic screening

Confirmed duplicates that have been detected after data entry are usually managed through a merging process. By merging cases, usually a master case is created in a database, which refers to the case chosen or created to represent the duplicated information. When creating a master case it is important to capture the case-identifiers and the sources of the duplicated cases in the ICH-E2B(R2) data field ‘A.1.11’/ICH-E2B(R3) data field ‘C.1.9.1’.

VI. Add I.4.1.1. Allocation of a master case

The allocation of a master case refers to the procedure where one of the confirmed duplicate cases is allocated as the master case and retains its classification as a valid case. The master case should support all pharmacovigilance activities such as signal detection and medical review of ICSRs.

The allocation of a master case procedure necessitates the “invalidation/inactivation” of the subordinate duplicates. This means that subordinate duplicate cases remain in the database for the purpose of audit trails, but will not be used for any other pharmacovigilance purpose. Figure VI. Add I.1. provides a pictorial representation of the allocation of a master case.

Follow-up information received for any of the subordinate duplicate cases will need to be evaluated and, incorporated into the master case unless the same, or more precise, information is already present in the master case.

This concept is most suitable for:

• Organisations (e.g. marketing authorisation holders, regional pharmacovigilance centres) which mainly receive cases in non-ICH-E2B-format, and where manual data entry is performed for the majority of the cases; and/or
• When the duplicate detection process is taking place at the time of data entry.

The Worldwide unique case identification number (ICH-E2B(R2) data field ‘A.1.10.1’ or ‘A.1.10.2’/ICHE2B(R3) data field ‘C.1.8.1’) of the individual case that is allocated as the master case should be maintained. The other subordinate duplicate case reference numbers should not be reused, but should be recorded in the ‘Other case identifiers in previous transmissions’ (ICH-E2B(R2) data field ‘A.1.11’/ICH-E2B(R3) data field ‘C.1.9.1’).

When allocating the master case based on the identified duplicates either the case that was first received, the case that contains the most detailed information or the case that was already transmitted to external partners can be selected. If there is no significant new information (see GVP Module VI for clarification of significance regarding follow-up information), the master case does not need to be transmitted to external partners (e.g. competent authorities in Member States, EMA). Case identifiers from previously transmitted cases should always be considered as significant new information, however case identifiers from non-transmitted cases need not be considered as significant new information.

All subordinate duplicate cases and related ICSRs should be retained and there should be adequate cross-referencing between case files and/or database entries.

If follow-up information is received for any of the duplicated cases, the master case should be updated accordingly.

VI. Add I.4.1.2. Creation of a master case

The Creation of a master case refers to the procedure where a master case is created with a new Worldwide Unique Case Identifier (ICH-E2B data field ‘A.1.10’), based on all the information contained in the subordinate duplicate cases. All of these subordinates are flagged as duplicates and linked to the master case and remain valid for the purposes of receiving follow-up information; only the master case, will be used for pharmacovigilance activities such as signal detection and medical evaluation.

If there is no significant new information related to the case (see GVP Module VI for guidance on Follow-up information), the master case does not need to be transmitted to external partners (e.g. competent authorities in Member States, EMA). Figure VI. Add I.2. provides a pictorial representation of the Creation of a master case.

If follow-up information is received for any of the subordinate duplicated cases, they should be updated automatically based on the newly obtained ICSRs. All new information should be evaluated and the master case manually updated accordingly. This is the method employed in EudraVigilance.

This concept is most suitable for:

• Organisations (e.g. competent authorities in Member States, EMA), which mainly receive individual cases electronically in ICH-E2B-format from multiple Electronic Data Interchange (EDI) partners as it allows maintenance and traceability of all ICSRs as received originally from the Sender.

VI. Add I.4.2. Process maps and descriptions for allocation or creation of a master case

A detailed description of the process flow for the Allocation or Creation of a master case based on duplicates existing in a database is presented in the flowchart in Figure VI. Add I.3.

A detailed description of the process flow for the Allocation of a master case based on duplicates detected at the time of data entry is presented in the flowchart in Figure VI. Add I.4.. This process refers mainly to situations where a case has been reported on paper, and it has been identified as a duplicate of another case before any data has been entered in the local database.