Prevention of Future Deaths reports · 2019
Regulation 28 report to prevent future deaths, reference 2019-0500, written 20 Aug 2019. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.
| Date of report | 20 Aug 2019 |
|---|---|
| Reference | 2019-0500 |
| Deceased | Thelma Joyce |
| Coroner | Darren Salter |
| Coroner area | Oxfordshire |
| Category | Hospital Death (Clinical Procedures and medical management) related deaths |
| Source | judiciary.uk record · original PDF |
| Responses published | 1 |
Text recovered by OCR from a scanned PDF. OCR is imperfect: check anything you rely on against the source PDF. Reproduced verbatim, including the scan's own layout.
REGULATION 28 REPORT TO PREVENT FUTURE DEATHS THIS REPORT IS BEING SENT TO: 1. Mr Simon Stevens, Chief Executive Officer, NHS England, PO Box 16738, Redditch, B97 9PT CORONER lam Mr D M Salter, HM Senior Coroner for Oxfordshire. CORONER’S LEGAL POWERS | make this report under paragraph 7, Schedule 5, of the Coroners and Justice Act 2009 and regulations 28 and 29 of the Coroners (Investigations) Regulations 2013. INVESTIGATION AND INQUEST | conducted an inquest on 6 August 2019 at Oxford Coroners Court into the death of Thelma Joyce at the Churchill Hospital, Oxford on 14 February 2019. | gave a brief Narrative Conclusion as follows: ‘Thelma Joyce underwent necessary chemotherapy in January 2019 for gall bladder cancer but died due to toxicity and side effects caused by the chemotherapy drug, Capecitabine, and a DPD deficiency making her more vulnerable to severe side effects.’ Oxford University Hospitals NHS Trust (OUH) were represented at the inquest and Consultant Medical Oncologist, provided helpful oral evidence. | attach a copy of her witness statement dated 5 June 2019. Mrs Joyce’s family also attended the inquest. The main issue which they raised concerned the perceived failure to test Mrs Joyce for DPD deficiency prior to commencing chemotherapy. | received evidence that it was not routine to test patients who are due to receive the chemotherapy drugs Capecitabine and 5FU for DPD deficiency mainly because of the absence of a reliable test. However, | also received evidence that, with new technology and developments, there is now a reliable test. Indeed, OUH Trust now have a two-year pilot to test such patients. | attach a copy of my letter to OUH about this for your information. CIRCUMSTANCES OF THE DEATH Mrs Joyce commenced chemotherapy on 25 January 2019 but had a very severe reaction which led to her being admitted to the Churchill Hospital on 31 January and dying on i4 February despite treatment. The cause of death following post mortem was as follows: la Pneumonia | b Chemotherapy Toxicity | c Gall Bladder Cancer She was subsequenily found to have a DPD deficiency. HB s2ic if tne results of the DPD tesi had been known beforehand she would not have commenced Mrs Joyce on the chemotherapy because the risk was too great. |t is noted frorn paragraph 5 of the sialement that a person with oartial DPD deficiency will have low or very low leveis of the enzyme. If patients with DPD deficiency receive ihe chemotherapy drug Capecitabine, then there is a risk the drug will not be eliminated completely and thai the levels of the drug in the blood stream will be higher than normal and this can result in side effecis which can be more severe than usual. li is also noted that DPD deficiency can affect between 3-5% of people which is not an insignificant number. (| appreciate that up to 20% of neonle do nave severe side effects from Capecitabine and 5FU ard not all are DPD deficient). CORONER’S CONCERNS During the course of the Inquest the evidence revealed matters giving rise to concerns. In my opinion there is a risk that future deaths will occur unless action is taken. In the circumstances it is my statutory duty to make this report to you. The MATTER OF CONCERN therefore is in relation to the possible need for updated guidance in respect of testing for DPD deficiency for patients due to embark on Capecilabine and 5FU chemotherapy. It is reassuring that OUH NHS Trust have a two-year pilot in place to test for DPD deficiency. As far as | understand it, there are as yet no national guidelines or approved tests in respect of DPD deficiency. If it is the case that new technology and developments mean there is now a reliable test, | enquire if there should be guidelines issued concerning the use of a routine test. ACTION SHOULD BE TAKEN In my opinion action should be taken to prevent future deaths and | believe you have the power to take such action. YOUR RESPONSE You are under a duty to respond to this report within 56 days of the date of this report. | may extend the period on request. Your response must contain details of action taken or proposed to be taken, setting out the timetable for action. Otherwise you must explain why no action is proposed. COPIES and PUBLICATION | confirm that a copy of this report and your response will be sent to Mrs Joyce’s family. The Chief Coroner may publish either or both in a complete or redacted or summary form. He may send a copy of this report to any person who he believes may find it useful or of interest. You may make representations to me, the coroner, at the time of your response, about the release or the publication of your response by the Chief Coroner. Signed Date AG a 7D: Salter ee] lig HM Senior Coroner for Oxfordshire
1 response published against this report on judiciary.uk. A response is a body's written reply to the coroner's concerns; publication is at the discretion of the Chief Coroner's office, so an absent response does not mean nobody replied.
Mr D.M. Salter
Oxfordshire Coroner’s Office
The Oxford Register Office
2nd Floor
1 Tidmarsh Lane
Oxford
OX1 1NS
Professor Stephen Powis
National Medical Director
Skipton House
80 London Road
SE1 6LH
31st January 2020
Dear Mr Salter,
Re: Regulation 28 Report to Prevent Future Deaths – pneumonia due to
chemotherapy toxicity in consequence to gall bladder cancer (14 February 2019)
Thank you for your Regulation 28 Report dated 20 August 2019 concerning the death of
Thelma Joyce on 14 February 2019. Firstly, I would like to express my deep condolences
to Mrs Joyce’s family.
The regulation 28 report concludes Thelma Joyce’s death was a result of pneumonia due
to chemotherapy toxicity in consequence to gall bladder cancer.
Following the inquest you raised concerns in your Regulation 28 Report to NHS England
regarding the possible need for updated guidance in respect of testing for
dihydropyrimidine dehydrogenase (DPD) deficiency for patients due to embark on
capecitabine or 5FU chemotherapy.
Gall bladder cancer is a rare cancer and in the UK there are around 1,000 new cases
diagnosed each year. Where diagnosed at an early stage, surgical removal is the preferred
treatment and offers the potential of cure or long-term survival. In some cases, surgery is
supplemented with either chemotherapy or radiotherapy treatment. Where chemotherapy
is used, the medicines used are typically off label, i.e., licensed for another condition. This
is the case for both capecitabine and 5FU.
Where using off label medicines, Trusts are required to consider and agree internal
governance arrangements prior to treating patients. Both Trusts and individual prescribers
are also expected to have and adhere to policies relating to the safe prescribing and
monitoring of off-label licensed medications, including compliance with MHRA safety alerts.
written evidence sets out that the risks of treatment were explained
In this case,
and that Mrs Joyce received written material produced by Macmillan about capecitabine.
More broadly, both capecitabine and 5FU belong to a group of chemotherapy medicines
known as fluoropyrimidines. These medicines are known to present increased risks for
patients that have either a complete or partial DPD deficiency and, although very rare,
such complications can be fatal. While a complete deficiency is extremely rare and is
usually diagnosed in childhood, it is thought that between 2 and 8 in every 100 people have
a partial deficiency (Cancer Research UK).
NHS England and NHS Improvement
In relation to the matter of concern raised, evidence as to the adequacy of DPD testing has
hitherto been far from compelling, which is alluded to in your report. Underlining this, the
European Medicines Agency (EMA) in March 2019 began a review of the evidence for
testing and use of these medicines under Article 31 of Directive 2001/83/EC. Ultimately,
the review may result in changes to marketing authorisations of the relevant medicines
which would be mandatory. While these medicines are unlicensed for use in gall bladder
cancer, it would be normal practice for marketing authorisation requirements, such as for
testing and patient monitoring, to also apply to off label uses and would be managed
through Trust arrangements for off label medicines. The EMA review is not yet complete.
In England, the NHS Long Term Plan sets out the ambition and commitment to establish a
genomics service providing access to cutting edge genomic technologies which will help to
pave the way for wider advances, particularly in relation to personalised medicine. The
introduction of an effective testing strategy for DPD deficiency, to better tailor treatment
decisions to individual patients, is a clear example of this. To that end, I can confirm that
work to review the evidence for DPD testing is underway within NHS England and NHS
Improvement, with a view to reaching a decision about whether to routinely commission
DPD testing and include the testing within the National Genomic Test Directory. A decision
is expected to be made by April 2020 and, if approved, will be supported with a plan for
implementation in order to achieve equitable access to testing across England.
Alongside this, steps have been taken to ensure a supply of a medicine called uridine
triacetate within England. The medicine can sometimes reverse the complications of
serious toxicity following exposure to fluoropyrimidines, when it is administered within 96
hours of exposure. The treatment is not currently licensed in the UK or Europe and has
not, until recently, been readily available outside North America. An urgent policy
statement, setting out NHS England and NHS Improvement’s commissioning
arrangements for this medicine is expected to be published in March 2020.
In line with our normal practices, both the updated Test Directory and the urgent policy
statement will be published on NHS England and NHS Improvement’s website and Trusts
will receive written notification of changes.
Thank you for bringing this important patient safety issue to my attention and please do not
hesitate to contact me should you need any further information.
Yours sincerely,
Professor Stephen Powis
National Medical Director
NHS England and NHS Improvement
NHS England and NHS Improvement
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