James Hedge

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Andrew Barkley gE | 151 Buckingham Palace Road
Senior Coroner : London SW1W 9SZ
South Wales Central i fa fran “ : United Kingdom

Rock Grounds,
First Floor, Aberdare Powys
CF44 7AE

mbra.gov.uk

13 September 2016

Re: Wir James Michael HEDGE.
Dear Mr Barkley

| write with reference to your Regulation 28 report (dated 27 July 2016) following the inquest into the death of Mr
James Michael Hedge.

The referenced incident was reported to the MHRA on 5 February 2016 by Roche, the manufacturer of the insulin
pump.

During the investigation into the reported incident, MHRA received notification from Roche Diabetes Care in June
2016 that a Field Safety Corrective Action would be undertaken which would update the handling instructions and
user manual provided to users of the Accu-Check Insight Pump System and NovoRapid Pump Cart insulin
cartridges. A Field Safety Notice (FSN) was published on 6 June 2016 and sent to healthcare professionals and
patients who are registered Accu-Chek Insight users and those who have ordered associated consumable
devices and accessories.

In addition, MHRA conducted a further risk assessment and decided the manufacturer's safety message should
be reinforced through centralised communication channels to the healthcare service. On 15 August 2016 MHRA
published a Medical Device Alert (MDA) to ensure that healthcare providers were made aware of the new
instructions for changing the insulin cartridge and the importance of communicating the risk to the patient's health,
if the manufacturer's instructions are not followed. A copy of this MDA has been attached to this letter.
Furthermore a press release highlighting key action points was also issued by MHRA.

The MHRA investigation has not yet been concluded. Roche Diabetes Care has indicated that they are reviewing
technical enhancements to the design of the system. MHRA will monitor the progress of the manufacturer with
this long term preventative action plan.

In order to fulfil the requirements of the Medical Devices Directive and place a medical device on the market, the
manufacturer must provide sufficient information and instructions to enable users of the device to operate it in
accordance with its intended function. This should include any warnings and precautions to take and any
undesirable side effects. The manufacturer should take into consideration the training and capacity of the
intended user and, where appropriate, instructions should be provided in symbol form.

MHRA is not responsible for training healthcare professionals and patients; however, we issue device specific
guidance such as the MHRA Device Bulletin (DB) on infusion systems and general guidance on managing
medical devices. These documents address the need for healthcare professionals to be trained in the use of a
device prior to the use of the device (see appendices 3 and 4). We recommend health care professionals carry
out a risk assessment ensuring that the device is suitable for the patient and that adequate training and support is
available for users of the device.

MHRA raised awareness of the published MDA and manufacturer's FSN, which includes updated handling
instructions during the last National Medical Device Safety Officers’ (MDSO) Webex which took place on 7
September 2016. MDSOs are responsible for supporting local medical device incident reporting and learning.
The Webex is a joint MHRA/NHS initiative designed to improve communication and address medical device
issues,

MHRA has not identified a systemic problem relating to the inadequacy of instructions for use and product
labelling from other manufacturers of insulin delivery systems.

MHRA will continue to monitor the progress of the Roche Field Safety Corrective Action and will investigate any
further incidents that we receive. We conduct signal detection activities whereby incident reports received for any
given category of medical device are periodically reviewed.

Thank you for drawing our attention to this incident and | should like to assure you that MHRA always strives to
improve patient safety through the monitoring of adverse incidents with medical devices and by working with
manufacturers to improve design and the instructions for use of their products, as appropriate.

Yours sincerely

lan Hudson

Chief Executive

Devices Safety and Surveillance

Medicines and Healthcare products Regulatory Agency (MHRA)

151 Buckingham Palace Road, London, SW1W 9SZ, UK :

England

Professor Sir Bruce Keogh
National Medical Director
Skipton House
80 London Road
Mr Andrew Barkley SE1 6LH
Senior Coroner — South Wales Central
The Coroner's Office
1st Floor
Rock Grounds

Aberdare
CF44 7AE i24nSeptember 2016

Dear Mr. Barkley,
Regulation 28 report: James Michael Hedge

Thank you for your Regulation 28 report of 27 July 2016 regarding the sad death
of James Hedge. On behalf of NHS England | would like to express our
sympathy to the Hedge family.

NICE has advised" that insulin pump therapy should only be started by a trained
specialist team and that this team should provide structured education suitable
for people using insulin pumps.

NICE’s guidance on structured education’, which has just been updated and
reissued, cross-refers to the Department of Health’s Patient Education Working
Group report’. This advises that, in order for insulin pump therapy to be
successful, people with diabetes need to understand how to use the technology
and how to use insulin management skills, including structured self-testing.

Structured education from a specialist team for those who use insulin pumps
should therefore include education on the risk of diabetic ketoacidosis,
particularly if the insulin pump should malfunction or the device is not used
correctly. More generally, structured education should also cover the
management of hyperglycaemia, including supporting individuals to recognise
when hyperglycaemia may be arising, when and how to test for it, and what
action to take if ketone levels are elevated.

NHS England is currently reviewing how greater take-up and consistency of
structured education can be supported and the issues of key content in relation
to the risks from incorrect use of insulin pumps and the management of
hyperglycaemia will be considered as part of this.

| note that the Medicines and Healthcare Products Regulatory Agency (MHRA)

1 technology Appraisal 151 https://www.nice.org.uk/guidance/tal51
2 https: //www.nice.org.uk/guidance/qs6/chapter/Quality-statement-3-Structured-
education-programmes~for-adults-with-type-1-diabetes

http: //webarchive.nationalarchives. gov. uk/20130107105354/http: /www.dh.gov.uk/en/
Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4113195
High quality care for all, now and for future generations
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has also been asked to respond to your report. | understand that the MHRA has
recently issued a Medical Device Alert in relation to a specific brand of insulin
pump’, advising that ‘cartridges inserted incorrectly can leak insulin into the
cartridge compartment, resulting in an under-delivery of insulin, which may lead
to rapid deterioration of health, diabetic ketoacidosis or death’. The MHRA has
advised that this should be brought to the attention of all healthcare workers
responsible for patients who use such pumps and has set out a range of
distribution routes recommended to those responsible for circulation of its device
alerts. :

Taken together, the planned actions on structured education and the advice on
specific devices should help support a greater awareness of the risks in relation
to insulin pumps, and a greater understanding by healthcare professionals and
by patients of the steps they need to take.

Thank you for bringing this important issue to my attention. | hope that you are
reassured that this organisation is taking appropriate steps to address the
concerns as detailed in your report.

Yours sincerely
[Jt M

Professor Sir Brute Keogh KBE, MD, DSc, FRCS, FRCP
National Medical Director

NHS England

* https: //www.gov. uk/drug-device-alerts/accu-chek-insight-insulin-pump-system-
manufactured-by-roche-diabetes-care-with-novorapid-pumpcart-cartridges-risk-of-
hyperglycaemia

High quality care for all, now and for future generations

Mr. Andrew Barkley
Senior Coroner
South Wales Central
The Coroner's Office
ist Floor

Rock Grounds
Aberdare

CF44 7AE

14 September 2016

Dear Sir,

As the General Manager of Roche Diabetes Care Limited UK, I am responding on behalf of |
© your report to prevent future deaths issued on 27 July 2016, following the inquest into the
death of Mr. James Hedge.

In your report you raise two matters of concern. In our response, we describe the product information and
educational materials supplied by Roche and then proceed to respond to each of your concerns.

As a preliminary matter, please be aware that patient safety is our utmost priority. We have therefore
carefully reviewed our user manuals and training materials in response to the evidence given at the inquest as
well as to your matters of concern, In this response we focus on the Accu-Chek Insight insulin pump
system, the pump used by Mr Hedge. However similar information and training is provided in relation to
other Roche insulin pumps

Materials and information provided by Roche

The current materials provided to all users of the Accu-Chek Insight insulin pump system in the UK
comprises:

Device User Manuals
These are regulated documents, obliged to be supplied with the medical device to ensure its safe and effective

usage:
Roche Diabetes Care Limited Charles Avenue Tel. +44 (0}1444 256000
Burgess Hill
West Sussex
RH15 9RY

United Kingdom
Registration Number 9055599

e Accu-Chek Insight insulin pump Manual
© Accu-Chek Insight diabetes manager Manual
e Accu Chek Insight Diabetes Therapy System Manual

Additional Training documents
These are documents created by Roche to supplement the User Manuals and provide a comprehensive view
of the use of the device in the context of type I diabetes
© Accu-Chek Insight system Training Handbook Basic
© Accu-Chek Insight system Training Handbook Optional
e Accu-Chek Insight Pump Starter Guide
Welcome Pack
This is a third level of supporting information which includes summary information on the use of the
accessories provided with the Accu-Chek Insight insulin pump system
o Welcome letter
° Accu-Chek Insight Quick reference guides (8 topics)
© Charging your Accu-Chek Insight Handset
e Accu-Chek Monitoring Diary
© Accu-Chek Pump Starter Guide
e Accu-Chek Fastclix brochure
© Accu-Chek Insight Flex training guide
© A USB containing the Accu-Chek Insight training handbooks (Basic and Optional) and e-learning
modules

This material includes comprehensive information and warnings relating to the occurrence of
hyperglycemia, its prevention, symptoms and management. Please find attached at Annex A to this response,
a document which sets out the information contained in the documents supplied by Roche on the following
topics;
- the risks of hyperglycemia
- how to react in case of a hyperglycemic situation and diabetic ketoacidosis
the correct handling of the insulin cartridge
- the incremental risk where the cartridge is not inserted correctly or in the context of any other
misuse.

The welcome package contains a personal workbook (Accu-Chek Insight Pump Starter Guide)

where the patient can fill out their individual data during the training and pump set-up session by the
healthcare professional or diabetes specialist nurse. This was specifically designed to support healthcare
professionals and diabetes specialist nurses in educating their patients. This personal workbook (Accu-Chek
Insight Pump Starter Guide) includes explicit information about treating, correcting and preventing
hyperglycemia and ketosis. Details can be found under the heading “Hyperglycemia” in Annex A.

All the materials mentioned above were provided to James Hedge at the time of his initial training on Accu-

2/6

Chek Insight. The only addition to these materials is the Field Safety Notice which reinforced instructions
for insertion of the cartridge — this was supplied to all Accu-Chek Insight pump users who are registered with
Roche and to relevant Healthcare Professionals in May 2016.

In addition to the above, the Accu-Chek Aviva Insight Diabetes Manager, (which is the handset component
of the Accu-Chek Insight pump system) has compulsory hyperglycemia warning screens to remind the user
to check ketones, blood glucose concentration and insulin when they experience a high blood glucose
reading, This is an additional measure to support the patient in following the clinical actions recommended
by their healthcare professional in such a circumstance.

were
HIBS weming

Consider checking 4G,
ketones, ardirsutn

Overall, the content included in the documentation listed above, including the reinforced instructions in the
Field Safety Notice, the explicit warnings on the consequences of misuse as well as the additional warnings
and instructions on the device itself provide a comprehensive cohort of information to pump users. This
information, incorporating detailed device instructions and warnings and statements of risk, as well as the
provision of extensive training information applies across the Accu-Chek portfolio to all Roche insulin pump
systems.

In addition to the handling instructions and information materials that Roche Diabetes Care provides to all
pump users, we offer a round-the clock technical support phone line that patients can contact to resolve
technical issues and, where necessary to request next day deliveries of replacement devices and accessories, It
is important to consider however that, as a manufacturer of medical devices, it would be inappropriate for us
to provide individual therapy guidance to people with diabetes on insulin pump therapy. So for individual
clinical matters we ask users of our Accu-Chek products to always contact their GP, diabetes specialist nurse
or other treating healthcare professional, for guidance and advice.

Response to your matters of concern

1) Advice and guidance in relation to the use of the insulin pump and dangers of misuse

Your report states: “The evidence showed that the advice and guidance in relation to the use of the insulin
pump, which is one of several on the market, does not adequately highlight the dangers of misuse and the
potential consequences which may follow if the device is not used correctly - in this case, the incorrect
insertion of the insulin cartridge leading to a leak and loss of insulin at a time when blood sugars were high”.

3/6

Roche Diabetes Care considers that information relating to hyperglycemia, diabetic ketoacidosis and
associated clinical conditions should form part of the fundamental clinical training that all insulin patients
should receive from their healthcare professional. Such advice is an important component of basic diabetes
education and must have been provided to all insulin patients as a precondition for the use of our pump (see
Accu-Chek Insight insulin pump user guide / preface). The patient information leaflet accompanying the
insulin cartridge also includes similar information provided by the manufacturer of the insulin, By way of
example, Novo Nordisk advises users of NovoRapid PumpCart:

“Before using NovoRapid’ PumpCart® in a pump, you must have thorough training in the use of the
pump and information about any actions to be taken in case of illness, too high or too low blood sugar
or failure of the pump. Follow your doctor’s instructions and advice about the use of NovoRapid®
PumpCart® in the pump.”

The clinical information provided to patients by Roche Diabetes Care (and by other companies) in relation
to the effects and management of diabetes, including the proper response to hyperglycemia and the risks
associated with a high blood glucose, is therefore intended to supplement and reinforce the information
provided to the individual patient by healthcare professionals, but not to act as a substitute for such
information. Roche is not in a position to provide information on clinical matters tailored to the medical
condition and personal circumstances of particular patients and it would not be appropriate for us to seek to
do so.

Nevertheless, as indicated by the information provided in Roche documents and referenced at Annex A,
Roche supplies substantial generic (non-personal) information to users of its pumps in relation to the issues
raised in your first matter of concern, including the following topics:

e Advice about checking blood glucose regularly

° Advice on preventing, treating and correcting hyperglycemia including the need for prompt action

e Advice on preventing, treating and correcting ketosis including the need for prompt action

e Advice on how to insert the cartridge correctly

© Advice to consult with HCP for correct therapy settings

We believe this information is clear and comprehensive, to the extent that general clinical information may
properly be supplied to patients by a pump manufacturer.

With respect to the potential consequences of misuse, incorrect insertion of the insulin cartridge and the
risks of insulin leakage are explained in the information provided to patients (see heading “Correct cartridge
change” in Annex A) and are also addressed in the training provided to patients who commence on the
Accu-Chek Insight insulin pump system. Roche additionally issued a Field Safety Notice (FSN) on May 30,
2016 (the patient version of the FSN is attached as Annex B) which reinforced the existing advice on correct
insertion of the insulin pump cartridge in our Accu-Chek Insight insulin pump system and further
emphasized the risks related to incorrect handling. This FSN was provided to all current users of Accu-Chek
Insight, relevant HCP’s and is included with all new pumps dispatched. From October 2016, the reinforced
information set out in the FSN will be incorporated in the Accu-Chek Insight insulin pump product manual

4/6

provided with all new pumps.

The education of diabetic patients

Your report states: “The evidence showed that the education of diabetic patients does not adequately focus
upon the potential consequences of failing to properly manage a hyperglycaemic state and in particular, how
quickly such a state can become life threatening”.

As explained above, Roche strongly believes that education on diabetes, its symptoms and proper
management should be directed by treating health professionals in the context of the needs and wishes of the
individual patient. Knowledge of such matters are necessary for any patient with insulin dependent diabetes,
irrespective of whether they are treated using an insulin pump or through injections.

However Roche provides educational material to patients regarding these issues, as set out in Annex A, to
supplement the information provided by the patient’s health professionals.

In respect of your second matter of concern, we specifically dedicate a portion of our pump starter guide to
addressing hyperglycaemia - its causes, symptoms, risks prevention and treatment. This information is
provided to all patients and should be considered by them, prior to commencing use of the Accu-Chek
Insight insulin pump system.

In addition, where asked to do so by the local NHS, Roche provides training, together with an NHS diabetes
nurse specialist, to patients commenced on its insulin pumps. These training sessions address use of the
insulin pump, including the appropriate response to hyperglycemia. In all cases where a Roche
representative is invited by the patient’s healthcare professional to participate in the training of a new pump
user, the educational material provided by Roche would be specifically discussed as part of a patient’s
introduction to the device and its use.

As part of our Field Safety Notice we initiated updates to the pump training sessions with immediate effect.
This focused on the use of the new Training Handling chart (see Annex B) as part of the reinforced
instructions for correct insertion of the insulin cartridge.

In summary, Roche provides extensive, detailed information to patients, in relation to the use of our insulin
pumps, through a range of documents and educational methods, including user manuals, training materials,
face-to-face training sessions, integrated device warnings and a round the clock technical support telephone
service. In addition, as part of our on-going continuous post market surveillance program, we also issue Field
Safety Notices when information needs to be communicated or emphasized to our customers.

Action taken
We therefore believe that the information and training provided by Roche is detailed and comprehensive and

advises patients on use of the insulin pump and watns of the risks associated with misuse, including the
proper response to hyperglycaemia, to the extent appropriate from the pump manufacturer.

5/6

In the context of reports of incorrect insertion of the insulin cartridge into Accu-Chek Insight insulin pumps
including the case of Mr Hedge, Roche issued a FSN, which aimed to reinforce existing information on
appropriate insertion. These reinforced instructions will be inserted in the user’s manual for the product
from October 2016.

Finally, Roche keeps its product information and training methods under constant review and we would
welcome the opportunity to work more closely with the NHS to improve and reinforce our combined efforts

to educate patients and health care professionals in the safe and effective use of insulin pumps.

We hope that this letter answers your matters of concern, Please feel free to contact us should you require
further information.

Yours faithfully,

General Manager
Roche Diabetes Care Limited

cc: Dr. Ian Hudson - Chief Executive, MHRA
Dr. Andrew Goodall - Chief Executive, NHS Wales
Mr. Simon Stevens - Chief Executive, NHS England

6/6

Yr Adran lechyd a Gwasanaethau Cyyndelthasel
Cyfarwyddwr Cyffredinel a Prif Weithredwr, GiG Cymru

Pepartment for Health and Social Services

Director General and Chief Executive, NHS Wales . ccc san
Liywodraeth Cymru
Welsh Government

Mr Andrew Barkley
Senior Coroner
South Wales Central
The Coroner's Office,
ist Floor,

Rock Grounds,
Aberdare,

CF44 7AE

Our Ref: AG/AMC/SB

16 September 2016

Dear Wir Barkley
Regulation 28: Report te Prevent Future Deaths ~ lames Michael Hedge
‘Frank you fer your bringing to our attention the regulation 28 report follawing the

investigation into the death of James iael Heda. We have considered the concerns
carefully and are taking the following action.

and Healthcare Products Regulatory Agency (Miia)
and are awe y issued a Medical Device Alert, on the 15 August 2016, in response to
the concerns raised in your report. The Medical Device Alert raises awareness that
‘Cartridges inserted incorrectly can leak insulin into the cartridge compartment, resulting in
an under-delivery of insulin, which may lead to rapie deterioration of health, diabetic
ketoacidosis. or death’.

We have contacted the Medic

We are also aware that the manufacturers (Roche) of the insulin pump used in this
particular incident issued an urgent field safety notice in June 2016 in response to feedback
from people experiencing leaking insulin cartridges. The safety notice informs that handling
instructions will be updated in response to the feedback received and of the dangers the
under-delivery of insulin can lead to e.g. hyperglycaemia.

&X, BUDDSODDWYR | INVESTORS Pak at a at
‘od! MEWN POBL |IN PEOPLE eae AO 3NQ.—Gwefan o website: §

The urgent field safety notice has been sent to alt insulin pump teams and all people using
this pump to warn them of the potential for the cartridge to leak and updated handling
instructions.

The National Diabetes Delivery Plan for Wales recognises the importance of insulin pump
provision and structured diabetes education (SDE). With regard fo insulin pumps, the plan
cornmits health boards fo the provision of an insulin pump service in line with National
institute for Health and Care Excellence (NICE) guidance. As a result, our Diabetes
lrnplementation Group has identified insulin pump provision as one of its national priority
areas and has a specific line of activity aimed at health boards ensuring standards of safely
comply with NICE guidelines including annual education updates.

‘The national plan is currently being refreshed and extended to 2020; insulin pump provision
and SDE will remain key areas of priority in the revised plan which will be monitored by the
Diabetes Implementation Group.

| hope this reassures you of the action Welsh Government are taking.

Yours sincerely