Mohammed Hussain

Head Office 
Uffculme Centre 
52 Queensbridge Road 
Birmingham 
B13 8QY 

Date: 

4 September 2023 

Mrs Louise Hunt 
HM Senior Coroner for Birmingham and Solihull 
Steelhouse Lane, 
BIRMINGHAM B4 6BJ 

Dear Mrs Hunt, 

RE:   Prevention of Future Deaths Report for Mr Khalid Mohammed Hussian 
(deceased) 

Further to the Prevention of Future Deaths Report dated 12th July 2023, the Trust has now 
had an opportunity to review the Matters of Concern you have raised within the same. I would 
first like to begin by offering my sincere condolences to the Family of Mr Hussain for his very 
sad loss. As a Trust we have taken your concerns very seriously and have aim to act on these 
issues as quickly as possible to ensure lessons are learned to benefit other patients in the 
future. I will respond to each issue in turn; 

1.  Monitoring of clozapine levels 

All blood test results including plasma clozapine assays are  available from within Rio by a link 
to the 'ICE' results system provided by the laboratory.  

In addition, all raised plasma clozapine assay results are reported to a  specialist report that 
pharmacy  staff  have  access  to.  These  results  are  reviewed  by  the  trust  lead  clozapine 
pharmacists.    Where  appropriate,  the  lead  clozapine  pharmacists  contact  the  responsible 
clinician  and  team  manager  to  highlight  the  result  and  need  for  the  patient’s  clozapine 
treatment to be reviewed, particularly regarding dosage. It is especially important to ensure 
the result is ‘trough’ value i.e. the sample was taken around 12 hours following the last dose.  
This ensures accurate interpretation. 

A number of training elements are being planned: 

1. 

A recorded webinar by a consultant psychiatrist and pharmacist with significant 
experience in the use of clozapine will be taking place on 8 September 2023 and will 
be available for all clinical staff to improve the knowledge around clozapine including 

Customer Relations │ Mon – Fri, 8am – 6pm  
Tel: 0800 953 0045 │ Text: 07985 883 509      
Email: bsmhft.customerrelations@nhs.net 
Website: www.bsmhft.nhs.uk 

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interpreting plasma levels and what to do with them. This will also be available on the 
Trust Intranet for anyone who cannot attend on that date.  

Development of a series of e-learning modules on the trust e-learning platform form 
the  Learn  It  Online  resource    www.learnitonline.co.uk.  Clinical  staff  will  be  able  to 
access these as part of their on-going training to improve knowledge around clozapine. 
This  is  anticipated  that  the  team  will  be  able  to  take  this  to  the  Learning  and 
Development Team by September 2023.  

The  Trust  has  multidisciplinary  experts  on  the  subject  of  clozapine.  There  is  also 
expertise in the Pharmacy Clozapine Team; to support follow up of raised clozapine 
plasma  assays  but  more  importantly  to  support  all  teams  involved  with  the  use  of 
clozapine with training in the handling of clozapine and promotion of the trust clozapine 
prescribing  guidelines  and  procedures.  This  team  is  expected  to  be  established  by 
September 2023. All these colleagues will be made known to staff for any advice that 
is needed. Staff can also ask for help through their manager, who can signpost them 
accordingly. This will help improve the skills and experience in responding to results 
on  clozapine  levels  appropriately  with  the  care  of  the  patient  at  the  centre  of  all 
decisions. 

2.  Medication Changes 

As part of the learning there will be clear guidance on prescribing on the electronic system 
and communication of how best to do this when a dose change is required.  

Where a clinician may be new to the Trust there will be clear instructions to ask for support at 
the  time  of  need  and  the  line  manager,  team  managers  and  clinical  director  will  have 
processes in place to guide them to ensure they have the right advice. 

The  staff  involved  in  this  case  are  being  asked  to  have  reflective  conversations  around 
learning from this case.  

3.  How to record high clozapine levels 

All blood test results are made available to staff in the ICE system, which is provided to us by 
our  pathology  service  provider.  This  system  is  used  both  for  ordering  tests  and  reviewing 
results. It is accessed from within Rio and in patient context, so all staff have ready access to 
results. In common with most other systems, abnormal results are indicated within the system 
along with the normal reference range.  

Clozapine levels are the only lab result which have a mechanism of routine reporting of high 
levels with pharmacy review and as such it has the greatest safeguards around it of any test 
used by BSMHFT. 

The  additional  steps  which  are  also  mentioned  in  point  one  will  ensure  that  clinicians  will 
understand how to interpret results and actions are taken, in cases where this is necessary.  

4.  Understanding of clozapine 

The Training is aimed to be in place to ensure that staff are confident in the use of  clozapine 
and its monitoring in the future. We have sent an email to all prescribers about the need to 
record about decisions of care following a clozapine result that may be out of range, the need 
to ensure there is clinical review and this is documented. 

 
 
 
 
 
 
 
 
 
 
 5.  August 2020 Regulation 28 Report 

Following the last PFD in August 2020 the Trust made significant changes to the processes 
and procedures surrounding clozapine and its use. However this case has highlighted areas 
of learning. Consequently, the Trust has now put into place an urgent learning session along 
with future planned  training and development  to ensure staff keep up to date with this and 
learning is refreshed, alongside other additional support systems that have  previously been 
introduced.  

6.  Quality of internal investigation process 

Serious Incident investigations are carried out under the Serious Incident Framework (2015) 
and  are  conducted  for  the  purposes  of  learning  to  prevent  recurrence.  As  part  of  this 
investigation expert opinion was sought from our Specialist Clozapine Pharmacist; 

, which were included within the body of the RCA and reflect a number 

of the issues you have raised. 

As a Trust we would like to assure you that we have governance processes in place which 
provides  oversight  of  the  quality  of  our  serious  incident  investigations  and  input  into  the 
recommendations based on the learning the investigation has found. 

In this case the learning points were: 

•  The system for escalation of clozapine levels and monitoring and implementation of 

plan were not followed. 

•  Record keeping was not of a standard as expected. 
•  Clinicians  were  not  clear  on  coordination  of  prescribing,  ordering  and  delivery 
processes as part of EPMA and discussion via MDT was not used to clarify and ensure 
prompt action. 

•  There was a lack of understanding of how clozapine levels are to be interpreted and 

actioned. 

On this occasion the following actions were identified and carried out:  

•  For there to be a review of the governance processes for the management of clozapine 
using the safety summit approach. In the short term as a mitigator the pharmacy team 
have prioritised the reviewing of the assay levels and the communication to consultants 
•  To improve the quality of record keeping the division has been working to establish a 
set of MDT standards is therefore recommended that the lead for this  work provides 
an update to the local governance committee on progress and that the team manager 
ensures the projector is fixed and in the meanwhile alternative methods used to ensure 
this is done to a good standard. 

•  Given the service users care needs; a carers assessment should have been offered to 
the family. As a Trust this is a recognised area of improvement across all services and 
to  support  this  piece  of  work  there  will  be  a  review  of  the  carer  engagement  tool. 
However,  in  the  short  term  the  team  should  have  bespoke  session  from  our  carer 
engagement team. 

7.  Pharmacy Resourcing 

 
 
 
 
 
 
 
 
 
 
 As  already  mentioned  in  the  first  point,  the  Trust  is  developing  a  specialist  Pharmacy 
Clozapine  Team  which  will  be  closely  linked  into  the  trust  multidisciplinary  team,gro  which 
should assist in ensuring that any concerns in the future will be acted upon and that where 
areas are identified where there is a lack of understanding, this team can support with learning 
to ensure that Service Users receive the best possible care.  

Yours sincerely, 

Chief Executive

10 South Colonnade 
Canary Wharf 
London 
E14 4PU 
United Kingdom 
gov.uk/mhra

Mrs Louise Hunt 
Senior Coroner for Birmingham and Solihull 
50 Newton Street 
Birmingham 
B4 6NE 

6th October 2023 

Dear Mrs Hunt, 

Regulation 28 Report concerning Mohammed Khalid Hussain 

Thank you for your report dated 12th July 2023, in which you asked the Secretary of State for 
Health to provide a response to the Regulation 28 Report to Prevent Future Deaths following 
the inquest into the sad death of Mr Mohammed Khalid Hussain. Your request has been 
passed to the Medicines and Healthcare products Regulatory Agency (MHRA) as we are the 
regulator of medicines, medical devices and blood components for transfusion in the UK. We 
would like to extend our sincere sympathies to the family of Mr Hussain for their loss. 

Your report identified a number of matters of concern, including the following points relating 
to clozapine: 

1. 

2. 

3. 

4. 

There is no clear system for monitoring actual clozapine or clozapine levels and there 
is no safe system to communicate high levels of clozapine; 

In this case, the patient’s consultant indicated that clozapine should be reduced on 
the next prescription, and this was communicated by email, but this was not read or 
acted upon. You note that the inquest heard there was no safe system to effect 
medication changes; 

That clozapine and norclozapine levels are recorded in the pharmacy section of the 
records but there was no system in place for highlighting high clozapine levels; 

That there was a lack of understanding of when to measure clozapine levels, how to 
interpret high clozapine levels and how to respond to these; 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 5. 

6. 

You note that a Regulation 28 report was sent in August 2020 which identified that 
there was no system in place to ensure abnormal clozapine levels were escalated 
and acted upon and there was a lack of understanding of the importance and 
frequency of clozapine monitoring; 

You raise concerns about the quality of the internal investigation process and whether 
it can identify central issues in a particular case; 

7. 

That the processes within the pharmacy were not effective due to a lack of resources.  

The MHRA is an executive agency of the Department of Health and Social Care (DHSC) 
with responsibility for the regulation of medicinal products in the UK. The MHRA ensures that 
medicines are efficacious and acceptably safe, and that any possible side effects which have 
been recognised to occur with use of a medicine are appropriately described in the 
authorised product information. This comprises the Summary of Product Characteristics 
(SmPC, intended for healthcare professionals), labelling, and Patient Information Leaflet 
(PIL, provided to patients in each medicine pack). The SmPC is a source of advice for 
healthcare professionals (HCPs) on the safe and effective use of a medicinal product. 

We have considered the evidence provided and the circumstances leading to Mr Hussain’s 
death. It is noted that he was established on clozapine in 2004 and in October 2022 a 
decision was made to reduce his medication, but this did not occur. As you note, there is a 
well-established system in place for monthly monitoring of white blood cell count in patients 
who are receiving clozapine. 

The MHRA has previously been alerted to a fatal case involving clozapine toxicity. This issue 
was reviewed and considered by our expert advisory committee. In August 2020, the MHRA 
issued a Drug Safety Update article advising monitoring of blood concentrations of clozapine 
for toxicity in certain clinical situations (Clozapine and other antipsychotics: monitoring blood 
concentrations for toxicity - GOV.UK (www.gov.uk). These include when: a patient stops 
smoking or switches to an e-cigarette; concomitant medicines are prescribed which may 
interact to increase blood clozapine levels; a patient has pneumonia or other serious 
infection; reduced clozapine metabolism is suspected, or toxicity is suspected. The advice of 
the MHRA and the Commission on Human Medicines is that clozapine blood concentration 
monitoring should be carried out in addition to the required blood tests to manage the risk of 
agranulocytosis.  

It is important to note that the terms of the SmPC do not impose drug level monitoring and 
this is an optional measurement. Any monitoring of clozapine plasma levels is done on an 
individual basis due to inter-patient variability and the SmPC does not define safe upper 
limits. The SmPC highlights certain clinical situations when blood clozapine level monitoring 
is advised as outlined above. Clozapine is well known to be associated with cardiac toxicity 
and the SmPC lists extensive information regarding this, including cases of fatal myocarditis 
and myocardial infarction. 

Unfortunately, it is not within our remit to comment on the clinical care in specific cases. 
Similarly, we are not able to comment on the quality of the internal investigation process or 
pharmacy resourcing. We will continue to keep the issue of monitoring for clozapine toxicity 

 
 
 
 
 
 
 
 
 
 
 
 
 under close review, including reviewing Yellow Card cases and we will be writing to the 
marketing authorisation holders to investigate further thresholds for clozapine toxicity. 

Yours sincerely, 

Chief Safety Officer 
Medicines and Healthcare products Regulatory Agency