Clozapine and Haematologic Malignancies: Observational and Retrospective Study Using the WHO Pharmacovigilance Database

Study Overview
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Brief Summary
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Clozapine may lead to various adverse reactions, including neutropenia and agranulocytosis. This study investigates reports of lymphoma and leukaemias for clozapine in the World Health Organization's (WHO) global database of individual safety case reports (VigiBase).

Detailed Description
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Clozapine is responsible of a wide range of adverse side effects.The investigators use VigiBase, the World Health Organization (WHO) database of individual safety case reports, to identify cases of haematologic malignancies following treatment with clozapine.

Official Title
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Clozapine and Haematologic Malignancies: an Observational and Retrospective Study Using the WHO Pharmacovigilance Database

Conditions
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Lymphoma, Leukemia

Intervention / Treatment
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* Drug: Clozapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Case reported in the World Health Organization (WHO) database of individual safety case reports to 03/05/2019 Adverse events reported were including the MedDRA terms: Malignant Lymphoma (SMQ), Leukaemia (HLGT) Patients treated with at least one liable antipsychotic drug (ATC class N05A) Exclusion Criteria: Chronology not compatible between the drug and the toxicity
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Haematologic malignancies with clozapine<br>Cases reported in the World Health Organization (WHO) database of patients treated by Clozapine, with a chronology compatible with the drug toxicity | Drug: Clozapine<br>* Clozapine treatment<br>* Other names: Clozapine treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between clozapine and haematologic malignancies using a disproportionality analysis in Individual Case Reports involving at least one liable antipsychotic drug in Vigibase®. | Study the correlation between clozapine and haematologic malignancies by comparing the proportion of Individual Case Reports (ICSRs) of hematologic malignancies with liable clozapine with the proportion of ICSRs of hematologic malignancies with at least one liable antipsychotic. | Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| investigate a potential dose-dependent effect | To investigate a potential dose-dependent effect, we will collect the clozapine daily dose from all clozapine ICSRs. In ICSRs with liable clozapine, the clozapine daily dose in mg will be divided into quartiles. A disproportionality analysis will be performed to evaluate the effect of the clozapine daily dose on the reporting of lymphomas and leukaemia. A significant difference of proportion of reports of haematologic malignancies between each quartile will be researched. | Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ] | 
| Description of the clinical features of clozapine-related haematologic malignancies | Description of the clinical features (mean age, sex ratio, time to onset, daily dose) of clozapine-related haematologic malignancies according to the main clinical subtypes | Case reported in the World Health Organization (WHO) of individual safety case reports to March 2019 ] |