Dear Mr Longstaff, Re: Regulation 28 Prevention of Future Deaths Report in respect of Lilly Grace Proctor I write in response to your regulation 28 report dated 1 May 2024 regarding the very sad death of Lilly Grace Proctor. I would like to express my sincere condolences to Lilly’s family. We have reflected on the circumstances surrounding Lilly’s death and the concerns raised in your report. We note your concerns about a lack of guidance on venous thromboembolic disease in children and the lack of child specific screening tools to assist the detection of pulmonary thromboembolism. Following receipt of your report, senior clinical advisors within the patient safety team at NICE have reviewed the concerns raised. They have advised that incidence of VTE in children is low –1.4-2.1 cases per 100,000 children per year. This is much lower than the incidence in adults. In children, the most common risk factors for VTE are the presence of a central venous catheter (CVC) or conditions such as congenital cardiac disease. Other risk factors include inherited hypercoagulable state (as in this case), infection, trauma, immobility, malignancy, and chronic inflammatory conditions. Given the rarity of VTE in children, existing NICE guidance on VTE does not include children. Furthermore, the clinical manifestations of severe VTE (such as PE) in children are nonspecific and often mimic the clinical symptoms of other more prevalent diseases. Regarding a screening tool, there is no specific screening tool that we are aware of. The Wells score and the Caprini score (scores used in adults) have both been evaluated in different paediatric populations, but their performance has not been good, and they cannot be recommended. There is, therefore, no screening tool that NICE could recommend. We note you have mentioned child specific screening tools being developed in other countries, but our clinical advisors are not aware of these and have not seen them used in practice.

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In terms of screening for these conditions in relatives of people with inherited thrombophilia, this is also not straightforward, as there are advantages and disadvantages. There are some situations where knowing that a child has an inherited defect may improve medical decision- making, and may give an opportunity to educate about signs and symptoms of VTE, which could lead to earlier diagnosis (as in this case); or to provide targeted thromboprophylaxis in clinical situations where the risk of VTE is increased; and to promote lifestyle modifications to avoid other prothrombotic risk factors (eg, sedentary lifestyle, overweight/obesity, and smoking). Conversely, inherited thrombophilia testing during childhood may be inappropriate, given the low risk of a thrombotic event; interpretation of screening tests can be challenging and may result in misdiagnosis. There are also ethical concerns about testing in those who may not have the maturity or understanding to make an informed decision. Screening is also problematic in situations where there is no clear medical benefit to the individual being screened. Nevertheless, NICE will consider the issues raised in your report through our recently implemented organisation-wide approach to prioritisation and topic selection. This is overseen by a single prioritisation board that guides the selection and coordination of our guidance development. We will ask our prioritisation board to consider if guidance should be developed in this area. In line with our usual practice, decisions made by the prioritisation board will be published on the NICE website. I hope this response has helped outline our role and the reasoning behind our lack of guidance in this specific area and would like to reiterate my sincere condolences to Lilly’s family.

Dear Mr Longstaff,

Re: RCPCH Response to the Inquest Touching the Death of Lily Grace Proctor A Regulation 28 Report – Action to Prevent Future Deaths

Thank you for sharing your report with us regarding the tragic and untimely passing of Lily Grace Proctor. I have shared your report with other senior paediartic colleagues within RCPCH. The details have also been shared with the Association of Paediatric Emergency Medicine

We have read your report carefully and would like to offer a response to the matters of concern you have set out.

1. Screening tools to assist the detection of pulmonary thromboembolism / NICE Guidance NG158 “Venous thromboembolic diseases: diagnosis, management and thrombophilia testing”

We note your pertinent concerns that, in the absence of resources similar to those available when dealing with the adult population, clinicians working with children may be disadvantaged in diagnosing and treating the condition, to the obvious potential detriment of their patients. We would agree that this is the case.

We also note that the annual incidence of venous thromboembolism is very low in children, estimated at 0.07–0.49 per 10,000 children, making this a difficult diagnosis to make given the often insidious and non-specific early symptoms.

Paediatricians and other clinicians who see unwell children and young people could benefit from an effective tool to assist the clinical detection of pulmonary thromboembolism in children and young people. Also a national guideline on this topic that is specific to children could be helpful. We would look to the National Institute for Healthcare Excellence to take a lead on this work to help develop a further evidence base or consensus guidance in this complex area of clinical practice. If this is to be taken forward, the College would be happy to assist and provide clinical expertise.

2. Sharing information and learning for quality improvement across the paediatric community

RCPCH are currently reviewing our Emergency Care Standards and the information within your report has been shared with our Emergency Care Committee to inform this work.

The RCPCH Guideline Directory contains a full list of paediatric guidelines published by the National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN), as well as those from other Royal Colleges or paediatric specialty groups which meet the standards for RCPCH endorsement. If the above- mentioned paediatric guidance and screening tools are developed, they will be added to this directory to raise awareness across the paediatric community.

Our collegeis also responsible for supporting training and continuing professional development. We will ensure that the learnings from this tragic case are incorporated into any relevant courses, such as our course on How to Manage Non-Malignant Haematology.

The College will be sharing information and suggestions for local improvement from your report with our paediatric members via its patient safety portal. The anonymised information within your report, and anticipated response from NICE, will also be shared for discussion with the RCPCH Clinical Quality in Practice Committee, where further actions may be identified.

Thank you for seeking our views and reminding us of the importance of this work. Our sincere condolences are with Lily’s family.