VI. Appendix 5 Nullification of cases

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VI. Appendix 5

General principles regarding the nullification of cases are outlined in VI.C.6.2.2.9.

Table VI.11. Examples of scenarios for which cases should be nullified

Ex.	Scenario	Action
1	An individual case has been identified as a duplicate of another individual case previously submitted by the same sender.	One of the individual cases should be nullified. The remaining valid case should be updated with any additional relevant information from the nullified case. NOTE: In case of duplicate reports where one report needs to be nullified, the update of the remaining case should be performed in the form of a follow-up report65. Information on the identification of the nullified case(s) should be provided in the follow-up ICSR (Section ICHE2B(R2) A.1.11/ ICH-E2B(R3) C.1.9.1 ‘Other case identifiers in previous transmissions’).
2	A wrong ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ ICH-E2B(R3) C.1.8.1) was accidentally used and does not refer to an existing case.	The case with the wrong ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ ICHE2B(R3) C.1.8.1) should be nullified.
3	On receipt of further information it is confirmed that that the adverse reaction(s) occurred before the suspect drug(s) was taken.	The case should be nullified.
4	On receipt of further information on an individual case, it is confirmed that the patient did not receive the suspect drug(s). Minimum criteria for ICSR submission as outlined in VI.B.2 are no longer met.	The case should be nullified.
5	On receipt of further information it is confirmed by the same reporter that the reported adverse reaction(s) did not occur to the patient. Minimum criteria for ICSR submission as outlined in VI.B.2are no longer met.	The case should be nullified.
6	On receipt of further information it is confirmed that there was no patient for the individual case. The minimum criteria for an ICSR as outlined in VI.B.2 are no longer met.	If there is confirmation in a follow-up report that no patient was involved, the case should be nullified.

Table VI.12. Examples of scenarios for which cases should NOT be nullified

Ex.	Scenario	Action
7	A wrong ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ ICH-E2B(R3) C.1.8.1) was accidentally used. This wrong ‘Worldwide unique case identification number’ referred to a different existing case.	The report with the wrong ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ ICHE2B(R3) C.1.8.1) should not be nullified. An amendment report should be submitted to correct the information previously submitted. A new ICSR should be created and submitted with the correct ‘Worldwide unique case identification number’.
8	On receipt of further information on an individual case, it is confirmed that the patient did not receive the marketing authorisation holder’s medicinal product. However, the patient received another suspected product (active substance) previously not reported and the minimum criteria for ICSR submission are still met.	The case should not be nullified. A follow-up should be submitted within the appropriate time frame. The case narrative should clearly indicate that the patient did not receive the company’s medicinal product. The new suspected medicinal product (active substance) should be specified in section ‘Drug information’ (ICH-E2B(R2) B.4/ ICH-E2B(R3) G.k) of the ICSR.
9	On receipt of further information the reporter has confirmed that the reported adverse reaction is no longer considered to be related to the suspect medicinal product(s).	The case should not be nullified. A follow-up report should be submitted within the appropriate time frame with the updated information on the case. ICH-E2B(R2): Section B.4.k.18 ‘Relatedness of drug to reaction(s)/event(s) (repeat B.4.k.18.1 through B.4.k.18.4 as necessary)’ should be populated as necessary. ICH-E2B(R3): Section G.k.9.i ‘Drugreaction(s)/ Event(s) Matrix (repeat as necessary)’ should be populated as necessary.
10	On receipt of further information on an individual case, it is Change of the individual case from serious to non-serious (downgrading).	The case should not be nullified. A follow-up report or an amendment report (depending on whether new information was received or not) should be submitted: ICH-E2B(R2): the data element A.1.5.1 ‘Seriousness’ should be populated with the value ‘No’ without selection of a value for the data element A.1.5.2 ‘Seriousness criteria’. The data element A.1.9 ‘Does this case fulfil the local criteria for an expedited report?’ should remain populated with the value ‘Yes’. ICH-E2B(R3): the data element E.i.3.2 ‘Seriousness Criteria at Event Level’ should not be populated if the reaction is not serious. The data element C.1.7 ‘Does This Case Fulfil the Local Criteria for an Expedited Report?’ should remain populated with the value ‘Yes’
11	The primary source country has changed, which has an impact on the convention regarding the creation of the ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ICHE2B(R3) C1.8.1).	The case should not be nullified. ICH-E2B(R2): The data element A.1.0.1 ‘Sender’s (case) safety report unique identifier’ can be updated on the basis of the new primary source country code. However, the data element A.1.10 ‘Worldwide unique case identification number’ should remain unchanged. If, for some technical reason the sender’s local system cannot apply this policy, then the sender should nullify the original case. A new case should be created using the data element A.1.10 with a new ‘Worldwide unique case identification number’ reflecting the changed primary source country code. The ‘Worldwide unique case identification number’ of the case that was nullified should be reflected in section A.1.11 ‘Other case identifiers in previous transmissions’. ICH-E2B(R3): The data element C.1.1 ‘Sender’s (Case) Safety Report Unique Identifier’ can be updated on the basis of the new primary source country code. However, the data element C.1.8.1 ‘Worldwide Unique Case Identification Number’ should remain unchanged. If, for some technical reason the sender’s local system cannot apply this policy, then the sender should nullify the original case. A new case should be created using the data element C.1.8.1 with a new ‘Worldwide Unique Case Identification Number’ reflecting the changed primary source country code. The ‘Worldwide unique case identification number’ of the case that was nullified should be reflected in the data elements C.1.9.1 ‘Other Case Identifiers in Previous Transmissions’.
12	The suspected medicinal product belongs to another marketing authorisation holder (e.g. a product with the same active substance but marketed under a different invented name).	The case should not be nullified. It is recommended that the initial sender informs the other marketing authorisation holder about this case (including the ‘Worldwide Unique Case Identification Number’ (ICH-E2B(R2) A.1.10/ ICH-E2B(R3) C.1.8.1). The original organisation should also submit a follow-up report to provide this new information. The other concerned marketing authorisation holder should create a new case and specify the reference case number and the name of the initial sending marketing authorisation holder (ICH-E2B(R2) section A.1.11/ ICH-E2B(R3) section C.1.9.1‘Other case identifiers in previous transmissions’).
13	The suspected medicinal product received by the patient does not belong to the marketing authorisation holder (same active substance, the invented name is unknown and the report originates from a country, where the marketing authorisation holder has no marketing authorisation for the medicinal product in question).	The case should not be nullified. The marketing authorisation holder should submit a follow-up report with this information within the appropriate time frame.
14	The case is mistakenly submitted by the marketing authorisation holder A although the marketing authorisation holder B as co-marketer is responsible for the submission of the case.	The case should not be nullified. An explanation should be sent by the marketing authorisation holder A to the co-marketer B that the case has already been submitted. The marketing authorisation holder B should provide any additional information on the case as a follow-up report with the same ‘Worldwide unique case identification number’ (ICH-E2B(R2) A.1.10/ ICH-E2B(R3) C.1.8.1).