PFD report

Sasha Drysdale · Prevention of Future Deaths report

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Issued 18 Jul 2024•Manchester South

Report record

Published report and response evidence

This page connects the concerns raised in this report with statements found in recipients’ published responses. A link shows a clear evidence connection; it does not assign responsibility.

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Concerns
1

Raised in this report

Recipients
4

Named on the report

Responses found
5

Of 4 recipients

Stated actions
5

Described in responses

Recipients and published responses

Source document

Full report text

This is the full text from the original published report.

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Concerns and recipient responses

Select any concern, action or position to view the source wording.

Concerns raised1

  1. Potential increased risk of certain blood cancers among patients taking Clozapine
    Part of recurring concern: Unreliable safety monitoring and guidance for clozapine treatment
Responses linked to these concerns

Each statement is shown once, even when linked to more than one concern.

Actions described in response An action is something a recipient says it has done, is doing, or plans to do in response to a concern raised.4

  1. Action

    Complete a signal-validation and assessment exercise on potential associations between clozapine and haematological malignancies, including literature and safety-data analysis.

    Stated by Viatris UK Healthcare LimitedStated completedThe respondent said that this action was complete when they made their response on 31 July 2024.
  2. Action

    Conduct routine pharmacovigilance, including case-report monitoring, literature review, signal assessment, regulatory reporting and periodic safety updates, with continued safety-profile assessment.

    Stated by Viatris UK Healthcare LimitedStated completedThe respondent said that this action was complete when they made their response on 31 July 2024.
  3. Action

    Continue pharmacovigilance activities, including collecting and evaluating safety information and monitoring Zaponex’s safety profile.

    Stated by Leyden DeltaStated completedThe respondent said that this action was complete when they made their response on 31 July 2024.

Respondent positions A position is what a recipient says about a concern when it does not describe a specific action.7

  1. Position

    NIHR, rather than NICE, is responsible for clinical research into clozapine and related safety risks.

    Stated by National Institute for Health and Care ExcellenceRedirects responsibilityThe respondent said that another organisation was responsible for deciding or taking action.

Source evidence

How this individual concern was interpreted

PFD Monitor created a concise, searchable interpretation from the report wording shown below. Response links show a clear evidence connection; they do not assign responsibility.

PFD Monitor interpretation

Potential increased risk of certain blood cancers among patients taking Clozapine

Wider context from the report

“The court heard evidence as to a small number of studies conducted internationally which, whilst having small sample sizes, could be read as suggesting an increased incidence of certain forms of blood cancer amongst those taking Clozapine. I am concerned that further research is needed to either refute or confirm whether or not taking Clozapine materially increases the risk of a patient developing certain blood cancers. ”

Is this part of a recurring concern?

Yes — Unreliable safety monitoring and guidance for clozapine treatment.

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Complete a signal-validation and assessment exercise on potential associations between clozapine and haematological malignancies, including literature and safety-data analysis.

Verbatim wording from the response

“3.9 As part of Viatris’ pharmacovigilance activities for the Product, if any new safety information (showing potential correlation between the Product and a potential safety issue) is identified from any of the activities listed in paragraph 3.3, it triggers a process whereby Viatris will undertake a signal validation and assessment exercise in accordance with GVP module IX. This exercise involves a thorough analysis of ICSR data available in Viatris’ global safety database, data from clinical studies, worldwide scientific literature, review of major health authorities websites and their publicly available safety database globally to collect as much information to evaluate any potential evidence supporting any association between the Product and a potential safety issue.”

Source location

Response from Viatris UK Healthcare Ltd
Page 5 · response
Published 31 July 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Conduct routine pharmacovigilance, including case-report monitoring, literature review, signal assessment, regulatory reporting and periodic safety updates, with continued safety-profile assessment.

Verbatim wording from the response

“Viatris has a robust pharmacovigilance system in place in respect of all of its products, including Clozaril®. All reported suspected adverse reactions to the Product are evaluated by Viatris’ pharmacovigilance team (PV team). Viatris undertakes routine and continued monitoring of the benefit/risk balance of the Product.”

Source location

Response from Viatris UK Healthcare Ltd
Page 3 · response
Published 31 July 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Continue pharmacovigilance activities, including collecting and evaluating safety information and monitoring Zaponex’s safety profile.

Verbatim wording from the response

“Leyden Delta, as the marketing authorisation holder for Zaponex, has a pharmacovigilance and risk management system in place with processes for the continuous collection and evaluation of safety information. Leyden Delta takes proactive steps in conjunction with the regulatory authority when changes to the benefit/risk profile emerge.”

Source location

Response from Leyden Delta
Page 1 · response
Published 31 July 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Encourage and carefully review further research into clozapine and acute myeloid leukaemia.

Verbatim wording from the response

“Leyden Delta will continue to comply with its pharmacovigilance obligations and operating procedures for monitoring the safety profile of Zaponex. In particular we encourage, and will carefully review, any further research into clozapine (and indeed, AML) and we will not hesitate to take appropriate action should changes to the medicine’s safety profile emerge.”

Source location

Response from Leyden Delta
Page 2 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

NIHR, rather than NICE, is responsible for clinical research into clozapine and related safety risks.

Verbatim wording from the response

“Finally, NICE does not have a direct role in clinical research the UK; this is the role of the National Institute for Health and Care Research (NIHR). You may wish to contact them directly regarding any upcoming research on this subject area.”

Source location

Response from NICE
Page 2 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

MHRA, rather than NICE, should lead surveillance and investigation of clozapine’s safety and haematological malignancy risks.

Verbatim wording from the response

“In relation to the main issue that you have asked us to respond to, you may be aware that NICE is not the regulator for medicines and medical devices in the UK; this is the role of the Medicines & Healthcare products Regulatory Agency (MHRA). The MHRA is responsible for issuing the marketing authorisation for medicines (also known as the licence) and has ongoing responsibility for monitoring their safety.”

Source location

Response from NICE
Page 2 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Available evidence does not establish that clozapine increases the incidence of haematological malignancies.

Verbatim wording from the response

“3.11 As part of Viatris’ signal validation and assessment exercise, Viatris reviewed the literature and analysed the safety data that was relied upon in these two articles, and concluded that no causal relationship between haematologic malignancies and clozapine could be established by either study. This is consistent with the conclusions reached by the authors in both studies. When assessed holistically against the adverse event and safety information contained in Viatris’ safety database and the fact that there are no regulatory documents available on this topic, the signal was not validated (i.e. the “signal”: a potential link between an increased incidence of haematological malignancies and clozapine use, was not proven).”

Source location

Response from Viatris UK Healthcare Ltd
Page 5 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Ongoing pharmacovigilance and routine safety monitoring are considered sufficient, so no additional action is required.

Verbatim wording from the response

“3.12 Viatris’ assessment remains unchanged by the ongoing pharmacovigilance since the signal validation and assessment exercise in 2022. Accordingly no action is proposed.”

Source location

Response from Viatris UK Healthcare Ltd
Page 6 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

A causal relationship between clozapine and blood cancer has not been established or confirmed by current evidence.

Verbatim wording from the response

“A causal relationship between Clozapine therapy and blood cancer (leukaemia) is at the current state of scientific knowledge not established and therefore not referenced in the SmPC.”

Source location

Response from Britannia Pharmaceuticals Ltd
Page 2 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

The slightly increased blood-cancer risk associated with clozapine is outweighed by its overall reduction in mortality.

Verbatim wording from the response

“• A statistically calculated slightly increased risk of Blood Cancer in Clozapine patients is outweighed by the overall reduction in mortality by Clozapine treatment.”

Source location

Response from Britannia Pharmaceuticals Ltd
Page 3 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

There is no convincing evidence that clozapine causes acute myeloid leukaemia, and pharmacovigilance has identified no causal link.

Verbatim wording from the response

“In respect of the concern raised, concerning a potential for clozapine to cause AML, it is the considered position of Leyden Delta that there is no causal link between clozapine and AML. Neither we, nor the MHRA have identified such a link through pharmacovigilance. Upon receipt of your letter, Leyden Delta has additionally sought the expert opinion of their Consultant Haematologist,”

Source location

Response from Leyden Delta
Page 1 · response
Published 31 July 2024

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Other statements in published responses

These actions and other statements could not be clearly connected to one concern in this report.

Recipient-stated actions An action is something a recipient says it has done, is doing, or plans to do in response to a concern raised.1

  1. 1

    Maintain the Clozaril Patient Monitoring Service as the mandatory patient monitoring system for Product users.

    Stated by Viatris UK Healthcare LimitedStated completedThe respondent said that this action was complete when they made their response on 31 July 2024.

Recipient positions A position is what a recipient says about a concern when they do not describe a specific action.3

  1. 1

    The marketing authorisation holders lack the means and authority to prevent deaths of the type described in the report.

    Stated by Britannia Pharmaceuticals Limited and STADA Arzneimittel AGUnable to actThe respondent said that a constraint prevented them from taking the relevant action.
  2. 2

    Existing SmPC precautions and pharmacovigilance measures are considered sufficient to manage preventable risks from clozapine.

    Stated by Britannia Pharmaceuticals Limited and STADA Arzneimittel AGExisting arrangements considered sufficientThe respondent said that existing arrangements were sufficient, so no further action was needed.
  3. 3

    The MHRA is principally responsible for continuously monitoring clozapine’s safety profile and taking action when its benefit-risk profile changes.

    Stated by Leyden DeltaRedirects responsibilityThe respondent said that another organisation was responsible for deciding or taking action.

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Maintain the Clozaril Patient Monitoring Service as the mandatory patient monitoring system for Product users.

Verbatim wording from the response

“(a) Maintaining the CPMS, which is the mandatory patient monitoring service and a condition of marketing authorisation approval for clozapine.”

Source location

Response from Viatris UK Healthcare Ltd
Page 3 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

The marketing authorisation holders lack the means and authority to prevent deaths of the type described in the report.

Verbatim wording from the response

“• We as Marketing Authorisation Holders have no means and no power to prevent future deaths like that referred to in your report. We have measures in place that prevent those deaths caused by Clozapine that are to the best of our knowledge preventable.”

Source location

Response from Britannia Pharmaceuticals Ltd
Page 3 · response
Published 31 July 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Existing SmPC precautions and pharmacovigilance measures are considered sufficient to manage preventable risks from clozapine.

Verbatim wording from the response

“• Treatment with Clozapine is safe and effective, given that the indication and the precautions as defined in the SmPC are observed.”

Source location

Response from Britannia Pharmaceuticals Ltd
Page 3 · response
Published 31 July 2024

Open published response

Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

The MHRA is principally responsible for continuously monitoring clozapine’s safety profile and taking action when its benefit-risk profile changes.

Verbatim wording from the response

“Once a medicine is allowed to be placed on the market, the MHRA is principally responsible for continuously monitoring the safety profile of the medicine. This is known as pharmacovigilance. Patients, health professionals and pharmaceutical companies all contribute to pharmacovigilance activities. The MHRA will take action when changes to the benefit/risk profile become apparent based on its monitoring of multiple information sources, including spontaneous adverse drug reaction reporting schemes, clinical and epidemiological studies and reviews of worldwide published medical literature.”

Source location

Response from Leyden Delta
Page 1 · response
Published 31 July 2024

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Information checked against the published report and official responses · Data reviewed 7 Sep 2026 · About data quality and limitations

Data last updated 7 September 2026