15. Duplicate search in Pharmacovigilance

A duplicate case refers to the same individual case reported by different senders, through different routes to describe suspected adverse reaction(s) related to the administration of one or more medicinal products to an individual patient at a particular point of time. 

Common causes of duplicate reports are:

• A consumer and healthcare professional reporting the same event/reaction occurrence
• Multiple healthcare professionals treating the same patient reporting the same event/reaction occurrence
• An event/reaction occurrence being reported by the original reporter to both the MAH and the NCA
• Literature reporting of the same event/reaction occurrence for generics.

Impact of duplicate cases: 

Detection and handling of duplicates by National Competent Authorities (NCAs), Marketing Authorisation Holders (MAHs) and Sponsors of clinical trials (Sponsors) is an important element of good case management.

The presence of duplicates in any pharmacovigilance system can create misleading signals and therefore impact on the safety monitoring and potential regulatory actions. 

Example of duplication in the US FDA Adverse Events Reporting System (AERS) database: In an evaluation of quinine-induced thrombocytopenia, FDA researchers identified 20% of 141 reports as duplicates. (https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-new-risk-management-plan-and-patient-medication-guide-qualaquin)

Handling duplicate reports:

Handling duplicate reports typically involves three steps: 

1. searching/detection of duplicates 
2. confirmation of duplicates and 
3. management of duplicates. 

1. Searching/detection of duplicates: 

• Screening for duplicates should be done at the time when a new report arrives in the database.
• Every newly received ICSR referring to an individual case should be considered a potential duplicate and should be checked thoroughly against the cases that are already present in the database.

Duplicate search criteria: Different search criteria may be suitable for different datasets. The safety database offers lookup and duplicate detection features to assist the identification of an identical case during data entry procedures, based on automated and semi-automated search criteria. 

• Duplicate searches are generally performed based on similarities in patient, adverse reaction and medicinal product data. 
• Duplicate search can be performed by age, date of birth, gender, any patient identifier, suspected/interacting medicinal products and adverse events/reactions. 
• Adding ‘country’ to this search can be valuable, depending on the dataset. 
• If no match is found upon the initial search, the search can broadened e.g. by expanding the criteria to include null values (e.g. a new report concerning a female patient will be checked against other cases with a female patient cases and where the patient’s gender is unknown). 
• A search for duplicates can be based on the MedDRA Preferred Term (PT) level, but moving up to the associated Higher Level Term (HLT) or even HLGT (Higher Level Group Term (HLGT) might be appropriate. 
• For cases originating from clinical trials are usually well-documented and duplicate detection can include other criteria which will be more reliable, e.g. Research Centre ID and study details (protocol number, study ID). 
• If no match is found upon the final search then continue to create new case 

2. Confirmation of duplicate cases 

• Upon identification of potential duplicates, a manual confirmation will always be necessary. 
• A well- documented case, including a case narrative, is a prerequisite to confirm if two cases are duplicates.
• Judgement will always need to be applied especially for certain types of medicinal products and adverse reactions such as cases related to vaccines in ‘neonates/infants’ or widely used medicinal products amongst ‘elderly’ patients (e.g. vaccine reports in a ‘neonate’ with an adverse event of ‘injection site reaction’, even if the dates of administration, primary source, medical history and concurrent drug fields match, one can not be certain that reports are true duplicates as it is a common reaction possibly reported for many ‘neonates’ with similar history from the same clinic). 
• If there is conflicting or limited information, which on first review does not allow determination that the cases are duplicates, additional information from the reporter or sender needs to be sought. It is recommended to keep track of all duplicate investigations, also if cases are confirmed not to be duplicates. 
• If the individuality of cases cannot be confirmed without compromising legal expedited reporting timelines, it is recommended to enter the potential duplicated case into the database as a valid case. However, investigations to confirm or clarify the information submitted should be continued. Once the individual case is confirmed as a duplicate or otherwise, appropriate steps should be taken to manage the duplicates. 

3. Management of duplicate 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, or 
• The Master Case can be created as a new case combining the information from the subordinate duplicate cases.