Dear Mr Spinney,

NHS Devon acknowledges receipt of the Regulation 28 Report to Prevent Future Deaths following the inquest into the tragic death of William Northcott, case reference 744577. We extend our sincere condolences to William’s family and loved ones. This letter sets out NHS Devon’s response to the matters of concern you have identified. Matters of Concern and Responses

Concern 1: Approximately 40% of patients prescribed Clozapine under the care of Devon Partnership NHS Trust receive their monthly phlebotomy service via GP surgeries, often delivered by staff who may not be specifically trained in recognising Clozapine-related side effects. This may result in reduced opportunities to reinforce awareness of red flags and when to seek medical help. The Coroner notes this may also reflect a broader national concern. Response: In the 2025/26 financial year, NHS Devon will be cascading additional funding to Devon Partnership NHS Trust to support the implementation of more Clozapine clinics. This will increase capacity and allow more patients to receive their care from specially trained professionals. The clinics provide vital opportunities to reinforce education around Clozapine side effects and risks, including red flags and when to seek urgent medical attention. We believe this will reduce variability in patient care and improve overall safety for individuals receiving Clozapine.

2 Concern 2: William was found post-mortem to have significant cardiac abnormalities, including left ventricular hypertrophy, which had not been identified in life. While the risk of myocarditis is highlighted in policy, cardiomyopathies such as LVH receive less focus. ECGs may not be sufficient to detect these, and echocardiograms are not currently required at initiation or during treatment with Clozapine. The Coroner raised concern that similar risks may be present nationally. Response: NHS Devon is aware that clinical leads from Devon Partnership NHS Trust are in active discussions with the Royal College of Psychiatrists to consider new and emerging national evidence, including the findings set out in The Williams Protocol. NHS Devon will ensure that the outcomes of these discussions, and any changes to national policy, are shared and implemented within local systems. As a commissioner, NHS Devon is guided by national clinical standards and protocols. Should there be an update in national guidance concerning cardiac monitoring of Clozapine patients, NHS Devon will support Devon Partnership NHS Trust to implement those changes to improve patient safety. Concern 3: Patients with treatment-resistant schizophrenia typically receive support from multiple teams and agencies. During the inquest, it became apparent that communication between professionals was, at times, suboptimal. The Coroner seeks assurance that Devon Partnership NHS Trust is working to improve internal and cross-agency communication. Response: As this concern is directed specifically to Devon Partnership NHS Trust, NHS Devon has not provided a direct response. However, we remain fully committed to integrated working across systems and continue to collaborate with Devon Partnership NHS Trust and wider partners to promote high-quality, coordinated care for people with complex mental health needs. In summary, NHS Devon takes seriously its responsibility to commission safe and effective services. We are committed to working in close partnership with Devon Partnership NHS Trust and other agencies to address the issues you have raised and to ensure learning and improvements are made that will help prevent future deaths.

Dear Ms Wiltshire,

Regulation 28 Report into the death of William Antony Northcott

Thank you for your Regulation 28 Report relating to the death of William Antony Northcott. I would like to offer my sincere condolences to Mr Northcott’s family on their tragic loss.

I understand from your report that Mr Northcott’s death resulted from sudden cardiac arrhythmia caused by the combined effect of mixed drug toxicity with a background of an enlarged heart and left ventricular hypertrophy. Mr Northcott’s medication included clozapine and fluoxetine which were prescribed and maintained at therapeutic levels. Postmortem toxicological analysis also revealed amphetamine levels consistent with recreational use.

Clozapine, fluoxetine and amphetamine are all recognised to be cardiotoxic drugs and carry risk of causing sudden cardiac arrhythmia. Your report identified the following matters of concern relating to clozapine and fluoxetine.

1. That the discussion and repetition of information surrounding red flags and side effects associated with clozapine, and advice about when to seek medical attention, will be significantly more limited for those patients attending their GP practice than for those attending the monthly clozapine clinics under the care of Devon Partnership Trust, and that this may be a national issue.

2. That clozapine-related cardiomyopathies could go undetected in patients under the care of Devon Partnership NHS Trust who are prescribed clozapine and leave them at unknown increased risk of fatal cardiac arrythmias, and that this may be a national issue.

3. That communication from healthcare professionals at Devon Partnership NHS Trust of important issues to patients suffering from treatment resistant schizophrenia was not as clear as it should have been.

The Medicines and Healthcare products Regulatory Agency (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 information to aid the safe use of a medicine, including possible side effects are appropriately described in the authorised product information.

This information 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 product information can support discussions between healthcare professionals and patients. The PIL is not intended to replace the discussion with prescribers about the benefits and risks of treatments.

The current special warnings and precautions for use section of the SmPC for clozapine states within the sub-section relating to cardiovascular disorders:

“Analysis of safety databases suggests that the use of clozapine is associated with an increased risk of myocarditis especially during, but not limited to, the first two months of treatment. Some cases of myocarditis have been fatal. Pericarditis/pericardial effusion and cardiomyopathy have also been reported in association with clozapine use; these reports also include fatalities.”

“If myocarditis or cardiomyopathy is suspected, clozapine treatment should be promptly stopped and the patient immediately referred to a cardiologist.”

Cardiac disorders are also described in the ‘undesirable effects’ section of the SmPC of clozapine, which lists arrhythmias, cardiac arrest and cardiomyopathy as possible adverse reactions to the treatment with clozapine. In addition, the contraindication section states that clozapine is contraindicated in patients with “severe renal or cardiac disorders (e.g. myocarditis)”. The section on interaction with other medicinal products states that “Some of the other serotonin reuptake inhibitors such as fluoxetine, paroxetine, and, to a lesser degree, sertraline, are CYP 2D6 inhibitors and, as a consequence, major pharmacokinetic interactions with clozapine are less likely.” Similar messages can be found in the current PIL for clozapine.

We have considered the evidence provided and the circumstances leading to Mr Northcott’s death and acknowledge that most of your concerns relate to clinical discussions between a patient and their prescriber or via the clinical care delivered by the Trust. Unfortunately, the MHRA cannot directly address these points, as it is not within our remit to comment on the clinical care in specific cases.

The MHRA continuously reviews the safety of medicines on the UK market and take appropriate regulatory action as required. Currently, the MHRA is reviewing the product information for clozapine. As part of this review, we will be giving careful consideration to the information which is provided to healthcare professionals, patients and their families and carers, and whether this can be improved to provide greater clarity. We intend to engage with relevant stakeholders during this process to ensure the regulatory documents meet the needs of patients and prescribers. It is anticipated that this review of clozapine will be completed this year.

Should you have any further questions, please do not hesitate to contact my office:

Dear Ms Wiltshire Re. Mr William Antony Northcott – Regulation 28 report. I write in my capacity as Chief Nursing Officer at Devon Partnership NHS Trust (the Trust) in response to your regulation 28 report dated 27 January 2025. Can I first of all pass on my condolences to Mr Northcott’s family and friend’s. In your report you highlighted areas of concern to The Pembroke Medical Practice, Devon ICB, Medicines & Healthcare Projects Regulation Authority along with us Devon Partnership NHS Trust (DPT). In respect to the concerns pertinent to DPT I respond as below: (1) The inquest heard evidence that there should be regular repetition of information to patients suffering from treatment resistant schizophrenia about the risks and red flags associated with the side effects of taking Clozapine. Since William's death Devon Partnership NHS Trust has set up Clozapine clinics which provide the opportunity for staff who are familiar with the side effects associated with Clozapine to discuss these with patients attending for their monthly phlebotomy appointments (required for the purpose of monitoring their white blood cell count). At these appointments healthcare professionals will specifically ask patients about their smoking habit, caffeine intake, bowel movements, hypersalivation, sedation, nausea, incontinence, heartburn, infection, and medication changes, in addition to open questions about any other side effects a patient might be experiencing. I am also assured that Devon Partnership NHS Trust will be including additional questions to be discussed at this appointment surrounding recent physical illnesses, palpitations, chest pain, breathlessness and dizziness.

Currently around 60% of the cohort of patients prescribed Clozapine who are under the care of Devon Partnership Trust have access to these clinics. The other 40% will attend their GP surgery for their monthly Clozapine phlebotomy service. The phlebotomy service provided at a GP practice is usually an appointment with a non-qualified member of staff, who will not have been specifically trained in the side effects of Clozapine. I am therefore concerned that the level of care provided to patients attending Clozapine clinics on a monthly basis, is likely to be superior from the care provided to those patients who attend their GP practice. In particular, I am concerned that any discussion and repetition of information surrounding regular flags and side effects associated with Clozapine, and advice about when to seek medical attention, will be significantly more limited for those patients attending their GP practice than for those attending the monthly Clozapine clinics. I am also concerned that this limitation is likely to extend further than the 40% of patients in receipt of Clozapine under the care of Devon Partnership NHS Trust and that this may be a national issue. We recognised that there is variability in the quality and frequency of side effect screening and monitoring processes undertaking for patients prescribed Clozapine. There are around 230 patient that attend the DPT lead specialised Clozapine clinics where Physical monitoring and side effects screening occurs in accordance to the regularity of when blood test is required. This varies between weekly, two weekly or every 4 weeks. However, the 40 % that accounts for 160 patients that attend GP surgeries where the side effect monitoring and screening does not occur. For this group we will be implementing the following As a Trust we have developed a business case in order for the organisation to increase resources and to bring all the patients receiving Clozapine onto dedicated Specialist Clozapine clinics across Devon in Barnstaple, Exeter and Torquay (excluding Plymouth where Livewell provide mental health services) to receive the Gold Standard in Physical health monitoring and side effects screening. (2) At post mortem examination William was found to have a significantly enlarged heart and left ventricular hypertrophy. This was not known to those caring for William in life. Clozapine is a cardiotoxic drug, and is often used in conjunction with other drugs which may also have a cardiotoxic effect. The risk of myocarditis is reasonably well explained in Devon Partnership NHS Trust's policy documentation, but there is less of a focus on cardiomyopathies which would include left ventricular hypertrophy. I understand that the Trust's guidance is based on national guidance. Annual ECGs are required for patients prescribed Clozapine and questions about cardiac function will now be asked at monthly Clozapine clinics. However, I understand that ECGs are not a diagnostic tool used to assist in the diagnosis of cardiomyopathies such as left ventricular hypertrophy and that left ventricular hypertrophy can be asymptomatic. I also understand that an echocardiogram may be able to identify such cardiomyopathies, but that this is not currently required on initiation of Clozapine or routinely at any other time whilst a patient is taking Clozapine.

I am concerned that these cardiomyopathies could therefore go undetected in patients prescribed Clozapine and leave them at unknown increased risk of fatal cardiac arrhythmias, as occurred in William's case. Given that the Trust's guidance is based on national guidance I am concerned this may be a national issue. Following your concerns we have reviewed the evidence based regarding Clozapine physical health monitoring and will be continuing seeking expert opinions as regarding the screening for cardiomyopathy in unsuspected patients to decrease the risk of harm. Myocarditis has a number of clinically well-defined features that makes it slightly easier to be identified in earlier stages of prescribing. It is more likely to occur within the first 8 weeks of commencing Clozapine treatment, the frequency is in a 3% of patients. It is a highly suspected condition in patients that present with fever above 38 degrees, chest pain, a heart rate above 120 bpm and respiratory rate of 20/ min. At blood test a raised troponin and C - reactive protein (CRP) above 100 mg would support findings. The florid presentation is identifiable by trained health professionals triggering an alert to activate a sudden cessation of Clozapine and seeking medical review and treatment However the screening for cardiomyopathy for unsuspected patients is significantly difficult. The current evidence based does not support the use of echocardiography as a pre-monitoring requisite given the excessive cost that this will bring. The incidence of cardiomyopathy in people taking Clozapine has been cited as 0.02% of patients in the USA and 0.1% in Australia. This is 1 in 1000 to 1 5000 patients taking Clozapine. In the Australian study where the designed a protocol that included Echocardiography it was found that Echocardiography are not viable as a screening tool for cardiomyopathy [Murch S, Tran N, Liew D, Petrakis M, Prior D, Castle D. Echocardiographic monitoring for Clozapine cardiac toxicity: Lessons from real-world experience. Australasia Psychiatry 2013;21(3):258–
61. Search PubMed]. The prevalence of cardiac dysfunction in patients commencing Clozapine is high. Routine echocardiography is not useful in the detection of Clozapine-associated myocarditis. Although cardiomyopathy may be identified, it is rare and associated with significant treatment costs. Recommendations for routine echocardiographic monitoring should be re-examined It is recommended for the clinician to be alert of any sign or symptoms of congestive heart failure so that the appropriate referral for expert opinion is sought. The key symptoms are; new complaint of tiredness without obvious medication changes, leg swelling or ankle oedema, palpitation and or shortness of breath. Further Developments: We are in communication with the Royal College of Psychiatrists (RCPsych) seeking information regarding The William’s Protocol. We understand in a blog posted at the RCPsych that the William Protocol is a suite of measures worked between (sister of William) and the Royal College of Psychiatrists. It is stated in the article that these measures will ensure far stricter monitoring of Clozapine, education for clinicians, families and carers on red flag side effects, better physical care and alongside address the unfair prejudice faced by people with severe mental illness. In order to get a deeper understanding on what is proposed by the William Protocol we as an organisation will be meeting with the Royal College of Psychiatrists Presidential lead for Physical Health to gather further details. At present the national guidelines available to us do not recommend the routine use of echocardiography as a screening tool in patients to be treated or receiving Clozapine treatment.

(3) It is clear that patients suffering with treatment resistant schizophrenia are complex, and as such there are often a number of different agencies involved in an individual's care. In addition, there are often multiple members of the same team involved in an individual's care. During the inquest it became clear that, at times, communication of important issues was not as clear as it should have been. I note that Devon Partnership NHS Trust has significant training available for its staff and other agencies it engages with in relation to patients who are prescribed Clozapine. However, it would be of great assistance to understand what Devon Partnership NHS Trust is doing to ensure that optimum communication of key information is achieved within the community mental health team, and when dealing with its other agencies involved in a patient's care. Delivering mental health care for individual suffering Severe Mental Illness requires a multidisciplinary and multiagency approach, ensuring effective information sharing can be challenging at times. There are a number of steps that Devon Partnership NHS Trust has adopted to ensure effective information sharing between those involved in the care of the patients. DPT has adopted a new Electronic Patient Records (EPR) named SystmOne. This EPR is used by a significant number of others GPs surgeries (60%) in the county and when patients consent to information sharing it allows both primary and secondary mental health services to see the information entered. Meaning that the GP will have immediate access to the entry made by a Consultant Psychiatrist following a consultation and vice-versa. This is of tremendous importance as one can access physical health related and medication information. This of course requires the patient to consent information sharing and as already stated it is not used by all the GP practices. Of course EPR sharing does not constitute a communication device Secondary Mental Health services communicate with primary care by sending clinic letters or e- mails. This tends to occur following consultations, assessments, reviews or any other clinically relevant interaction with patients. As we developed and designed Systmone to meet the specific needs of the service we identified a number areas for improvements that can communication effective. Including  A single individualised Care Plan across all DPT services which supports ensuring that the plan provides all the information pertaining to the patient promptly and in one place.  Care Plans to be coproduced by patients together with the clinician and shared with family members and carers  Other agencies such as the voluntary service will be having access to Systmone and consequently have access to the information relevant to patients taking Clozapine and their care plans  Information regarding physical health and findings that requires action will require active communication escalation between clinicians with clear actions.

.I trust the above responds clearly to your questions,

Pembroke Medical Group response to the Report to Prevent Future Deaths related to the investigation into the death of William Northcott

We have reviewed the findings of the inquest undertaken into the death of William Northcott, and considered the concerns raised in the Report to Prevent Future Deaths issued to us. We share the concerns of the Coroner in that the patients attending Clozapine clinics could receive a higher standard of care than those attending their GP practices. For this reason, the Practice has withdrawn from the agreement with DPT to provide phlebotomy services (see letter dated 27/3/24). As stated in our previous correspondence, we had concerns that the psychiatric oversight provided by Devon Partnership NHS Trust for this cohort of patients fell below the service standard we would consider safe. We had concerns regarding the number of agencies involved in the monitoring and prescribing of clozapine, without sufficient responsibility being taken by one team. Clozapine clinics can give continuity of care for these patients and ensure that regular education and all appropriate checks are undertaken. We have noted the comments by the Coroner that an ECG is not as helpful a diagnostic tool as echocardiography to assist in the diagnosis of cardiomyopathies. We agree that the use of echocardiography for monitoring of patients on clozapine could be explored, as this is used in some other countries. Again, this is something that could not be undertaken in Primary Care as we do not have echocardiography. In response to the Coroner’s concern about a Health Care Assistant who may have less experience and knowledge of anti-psychotic medication seeing patients and undertaking the investigations required for annual monitoring, the Health Care Assistant will generally use a computer template to enter information, which can have prompts to ask relevant questions. This could be considered for those 40% of practices who are continuing to undertake clozapine monitoring. We use a template when undertaking the annual physical health monitoring required for all patients on our Severe Mental Illness register as mandated by the Quality & Outcomes Framework (NICE CG178 and NICE CG185). Following the Health Care Assistant appointment, there is a follow-up In Person or telephone call with a GP or trained clinician who reviews the results and undertakes a review of their Mental Health care plan. The Practice has ensured that all GPs and clinicians carrying out these appointments are made aware of the physical effects of clozapine/side effects to look out for. We do not usually share results of the health checks with the Mental Health teams, unless information is specifically requested. We agree however that good communication is very important. The practice would be happy to communicate the findings and results of the annual health checks with the Mental Health Services, providing that the patient has consented to this. We had considered involvement of the ICB and LMC to facilitate a streamlined approach. However, we have established that there is a Local Enhanced Service in place which we are currently reviewing and implementing a process to be able to share the outcomes and results from the annual review with Mental Health Services.

Clozapine monitoring has already been raised at the LMC, which resulted in many practices withdrawing from the agreement to provide monitoring services. I believe that this has led to the expansion of the clozapine clinics. The LMC secretary was notified of the concerns raised at the inquest on 14th January 2025 and we can request that it is raised again on the LMC agenda to encourage the further expansion of clozapine clinics. We have already highlighted the outcome of this case at our practice GP meeting on 12th February 2025 and provided education for GPs to remind them of the side effects of clozapine, particularly constipation/ smoking status and potential cardiovascular side effects. (see attached information sheet). We undertook an audit of all our clozapine patients in January 2024 to ensure that they had received the annual monitoring checks required for patients on our Severe Mental Illness register as mandated by the Quality and Outcomes Framework (NICE CG178 and NICE CG185). We plan to undertake a further audit and add an alert to the medical record to highlight to clinicians that they are taking clozapine. The timescale for this is for this to be completed by 1st April 2025. Dated: Signed: