UK Diagnostics Summit Presentations

Welcome
In Association with
#UKDiagnosticssummit

The key role of diagnostics in the
Antimicrobial Resistance challenge
Fiona Carragher
Deputy Chief Scientific Officer - NHS England

Fiona Carragher FRCPath @DepCSOFiona
Deputy Chief Scientific Officer for England
The key role of diagnostics in
the Antimicrobial Resistance
challenge
Nov 2017

The ‘neck and neck’ race of
antibiotic development - and resistance

The challenge of
21st Century antibiotic use
• 35,000 or 7% of all deaths in the UK are
caused by infectious diseases.
• 66 different antibiotics prescribed
- top 15 account for 98% in
general practice and 88% in
hospitals.
• 35 million courses of antibiotics
are prescribed by GPs in England
each year.
• Without antimicrobials, the rate of
post-operative infection for clean
surgery could be 0-50%. ~30% of
those with a serious infection would die.

The rising tide of
Antimicrobial resistance
• Infections are increasingly developing that we cannot treat with a
rapid spread of multi-drug resistant (MDR) bacteria
• We may not be able to treat of
prevent everyday infections or
disease
― Existing antimicrobials are
becoming less effective
― Bacteria, fungi, viruses are
adapting naturally and
becoming increasingly
resistant
― Inappropriate use of these medicines
― All-time low in new antibiotics
being developed
Recognising this is a ‘one health’ agenda
WHO priority list of 12 resistant bacteria that
pose the greatest threat to human health
www.who.int

The future if we do not act now
By 2050: more deaths from resistant infections than cancer

UK response to this challenge
Improving infection
protection and control
Optimising
prescribing practice
Improving
professional
education, training
and public
engagement
Developing new
drugs, treatments
and diagnostics
Better access to and
use of surveillance
data
Better identification
and prioritisation
Strengthened
international
collaboration
Progress against the strategy is reported on an annual basis

Leading worldwide action
on antimicrobial resistance
• UK Chief Medical Officer
Dame Sally Davies has led a
worldwide campaign to take
action on antimicrobial
resistance
• Sep 2016: 193 countries signed
a United Nations declaration
at the UN General Assembly
in New York
• For the first time, Heads of State
committed to taking a broad,
coordinated approach to address the root causes of AMR across
multiple sectors, especially human health, animal health and
agriculture.

Independent review of Antimicrobial Resistance - Jim
O’Neill
• Diagnostics are critical to the appropriate use
of antimicrobials
• Step change in the way technology is
incorporated into the decision making process
• Currently many decisions are based on an
empirical diagnosis
• Rapid point of care diagnostics enabling a
precise, timely diagnosis
• Decision support approach to drive change in
prescribing
“I call on Governments to ensure that, by 2020, all antibiotic
prescriptions will need to be informed by …. a rapid
diagnostic test wherever one exists” Jim O’Neill
“Having rapid, low-cost, and readily available diagnostics is
an essential part of the solution to this urgent problem.”
Dr Margaret Chan, DG, World Health Organisation
The role of diagnostics in AMR

Diagnostics
– the signalling system for the NHS
• Direct patients and patient flows
so that the right people get to
the right place at the
right time
• Ensure treatment and
management is efficient,
effective and coordinated
• Have a critical role in prioritising
activity so that services are resilient
and sustainable
• Fundamentally shape the health economics of particular patient
pathways

Which diagnostics
could be used in AMR?
• Bacterial or viral
• Bacterial type
• Resistance (which antibiotics
must I not use?)
• Susceptibility (which
antibiotics can I use?)
Recognising there is also a role
for host response biomarkers
From O’Neill http://amr-review.org/

National ambitions
1. Halve gram –ve HCAI blood infections by 50% by 2020
2. Halve inappropriate prescribing in humans by 2020
3. Reduce animal antibiotic use to 50mg/kg by 2018
4. Work internationally to bring new products to market
Infection
control
Optimised
prescribing
Diagnostics
Improved
animal use
Education & training
Surveillance, behaviour & evidence-based interventions
New approaches through discovery, innovation & global action

UK AMR Diagnostics - Vision
…..“This strategy will tackle the
issues around AMR through
patient-centred, cost effective
diagnostics by ensuring that the
right test is available at the right
place at the right time.
“It will maximise the use of
available technologies in human &
animal health sectors in the most
appropriate settings.”
The vision will be delivered through
a coordinated & consistent national
approach to standards & practice
• In every part of the country, in
every healthcare setting, the
same level of access to rapid
diagnostic technology &
digital antimicrobial guidance
tools are available
• The technology meets
nationally set standards of
quality & response times
• There is recognition that
different settings might need
different technical solutions
• Services are flexible &
responsive to the adoption of
new technologies that will
provide continuous improvement

UK AMR Diagnostics - Strategy
Ensuring that the right test is available at the right place at the right time.

Clinical
Pathways
Diagnostic
Stewardship
One Health Innovation
Policy and
Communication
Align to current
policy and
regulatory
environment
System partners
Public Health England
Health Education England
DEFRA
UK AMR Diagnostic Collaborative Programme
Key areas of focus

Putting diagnostics at the centre of AMR
management
A map of the Sepsis
pathway across home
and hospital
• Ideal Pathways
• Gaps and Opportunities
• Economic Modelling/Value
Proposition

Patient
presents
Condition
postulated
Test
ordered
Sample
Collection
Sample
processed
Reporting
Intervention
selected
Diagnostic stewardship
PRE-ANALYTIC POST-ANALYTICANALYTIC
DIAGNOSTIC
INPUT

Integration and collaboration
is everything
Academia
NHS
Patients
Industry
International
INVENTION EVALUATION ADOPTION DIFFUSION
Area of
maximum
advance

Innovation - opportunities through
new diagnostics
Point of care
testing
Handheld
‘lab on a chip’
High throughput
genomic
technologiesCoupling
smartphones with
‘lab on a chip’
technology for tests
eg gene arrays
Still at research
stage but show
great potential
Well established for
indirect technologies such
as CRP testing.
Developments in
microarrays offer
increased potential for
direct testing
Delivers rich direct testing,
allowing detailed
identification &
surveillance
Seeing advances in
speed of test and
reduction in cost

The system must be responsive
System
response
Define the
capabilities
Prioritise
technologies
Develop multiplex
systems
Supportive
regulatory
structure
Streamline &
develop evidence
base
Better availability of
test results

The power of diagnostics in AMR:
opportunities and challenges
Opportunities
Challenges
• Transforming existing
pathways and
approaches to support
new models of care
• Unpicking
commissioning of
diagnostics to focus
incentives
• Quality of data
available about current
use of diagnostics and
outcomes
• Constant evolution of
AMR requiring ongoing
innovation to keep up
• Next-gen diagnostics offer
a precise, timely
diagnosis – allowing the
use of the right drug in the
right place at the right time
• New settings for
diagnostics allowing near-
patient testing and greater
use of other clan
professionals (eg
Pharmacy)
• Commissioning levers
such as CQUIN, to drive
uptake of new approaches

How the NICE Office for Market Access (OMA) can
help the life sciences industry– overview of OMA
services
Ben Hendry
Outreach and Engagement Manager – NICE Office for
Market Access National Institute for Health and Care
Excellence

Ben Hendry, Outreach and Engagement Manager - NICE OMA
8th November 2017 – UK Diagnostics Summit (London)
How the NICE Office for Market Access (OMA) can help
the life sciences industry – Overview of OMA services

Product Development
The Evolving Landscape
Exciting times!.......
• Very strong pipelines of products with potential for major patient benefits
• Patients and healthcare systems need access to clinically and cost effective products as quickly as possible
• Personalised/precision medicine becoming a reality…
Challenges:
• High cost of some products
• Timely patient access while the evidence is still emerging
• New initiatives in the landscape
Effective engagement necessary to address challenges:
• The Office for Market Access
• NICE Scientific Advice
PRODUCT
ADOPTION
EMA
Adaptive
Pathways
PRIME
(EU)
MHRA
EAMS
(UK)
?
?
NICE Appraisals
& Highly
Specialised
technologies
NICE
Diagnostics &
Medical
Technologies
EMA/MHRA
(& notified
bodies)
INNOVATE
UK
NHS
ENGLAND
AHSNs
Accelerated
Access
Review
(UK)
DIT
Cancer
Drugs
Fund
(UK)
Life
Sciences
Strategy
PRODUCT
Evaluation

NICE Office for Market Access (OMA)
* Can be contacted directly
Product
Development
Product
Adoption
NICE
HTA
Opportunity to discuss your key system access questions along
the development to adoption pathway
Initial exploration with OMA team
Engagement
Meetings
Multi stakeholder
Focussed input
EAMSMulti
product
Under ‘Safe Harbour Principle’
Fee for service (not for profit)
External SignpostingInternal Signposting
e.g. NICE
SCIENTIFIC
ADVICE *
e.g. NIHR
FOR ALL TYPES OF LIFE SCIENCES TECHNOLOGIES
26

NICE OMA Engagement Meetings
• Supported by rules of engagement to ensure a
broad, open and free flowing discussion within
a confidential framework
• Collaborative event, with participation from a
range of relevant stakeholders
• Designed to provide the insights that help
companies deliver a patient & healthcare
system focussed market access plan
28

NICE Scientific Advice (NSA)
29
Provides
advice on
prospective
clinical and
economic
developmen
t plans,
which
helps
companies
generate
robust
evidence to
demonstrate
value, which
can be used
for future
NICE
evaluations
or in
discussions
with payers /
commission
ers
NICE scientific advice helps you to:
Think about the evidence you will need early enough to address it, i.e. before finalising the whole trial
programme
Understand pros and cons of different trial options – de-risking strategy
Explore alternative strategies to address data gaps
Integrate cost effectiveness considerations into early decision making

Medtech Early Technical Assessment (META) Tool©
• For developers of Medtech, the META tool can
help you to understand:
• Payer and commissioner requirements
• The evidence you will need to demonstrate
your value proposition
• The gaps in your current evidence
• Potential next steps
• For organisations that support Medtech
developers, the META tool provides:
• A structured framework to help Medtech
developers understand the evidence needs
of payers and commissioners
• A comprehensive educational package

Getting in touch with NICE OMA
Stay up-to-date with the latest from NICE:
Subscribe online to NICE News
https://www.nice.org.uk/news/nice-newsletters-and-alerts
Follow us on Twitter
@NICEcomms
www.nice.org.uk/OMA
OMA@nice.org.uk

How Diagnostics Are Being Used to Treat
Children
Dr Ann Van den Bruel
Associate Professor, Department of Primary Care
Health Sciences; Director of the NIHR Diagnostic
Evidence Cooperative, Oxford

Adding CRP point-of-care testing to
the management of acutely ill
children in primary care
Ann Van den Bruel
Director NIHR Diagnostic Evidence Cooperative
Associate Professor Nuffield Department of
Primary Care Health Sciences
University of Oxford

Serious infections in children
• Pneumonia
• Pyelonephritis
• Sepsis
• Meningitis
• Bacterial gastroenteritis
• Cellulitis
• Osteomyelitis

Serious infections in children
• Half are missed at first presentation
• Diagnostic uncertainty affects antibiotic
prescription rates
• CRP at the point-of-care
– Rule out serious infections?
– Guide antibiotic prescribing?

Diagnostic tools in primary care
• Observation, history, clinical examination
• Lab tests, imaging, ...
• ‘Watchful waiting’  safety netting
Setting
specific!

Rule out:
CRP < 20 mg/L
Procalcitonin < 0.5 ng/ml
Van den Bruel et al., BMJ 2011

Pilot study
• To collect input
parameters for a larger,
definitive trial
– Recruitment rates
– Tentative effect CRP on
referral rates, hospital
admission, additional
testing, antibiotic
prescribing rates
– Acceptability to parents
and health care staff
Cluster RCT
• To assess effect on
– Diagnosis serious
infections
– Antibiotic prescribing
– Referral and hospital
admission
– Additional testing

Design pilot study
• Cohort study with nested randomised
controlled trial
• One out-of-hours centre in Oxford, UK
• Sample size
– 700 children in cohort
– 350 in RCT

Standardised measurement of vital signs of acutely ill children, 1
month-16 years presenting to out-of-hours
Consecutive inclusion after consent, with subsequent application
of vital signs measurement on prediction score and centiles
R
CRP testNo CRP test
GP management
Outcome adjudication
Subgroup of children with temperature
≥38°C
Interviews with purposive sample of parents, and GPs and
nurses.

Procedures
1. Temperature measurement, CRP test
2. Regular clinical assessment
• GP
• Record immediate decisions
3. Follow-up interview
• PCHCS scientist
• Purposive sample parents + all nurses/GPs

Results
• N=200
• Consent rate 67.3%
– CRP test may have contributed to non-participation in 63
out of 97 children
• Acceptability parents/children very high
– Pain minor and transient
• Utility for clinicians
– Mixed views

Design cluster RCT
• Family practices in Flanders (Belgium)
• Acutely ill children 1 month – 16 years
• Clinical decision tree (gut feeling, dyspnoea,
temp ≥40°C, or diarrhoea in child 12-30 M):
– Positive: CRP test
– Negative: randomised to 1 of 4 groups
CRP test No CRP test
Brief safety net
intervention
A B
No brief
intervention
C D

Results
CRP in at-risk
children
CRP in all
Illness episodes, n 1417 1730
% positive on decision tree 20 20
Median CRP level 11 7
20 mg/L, sens/spec (%) 25/70 57/74
5 mg/L, sens/spec (%) 100/43 100/47

Results
CRP in at-risk
children
CRP in all
Had CRP test (%) 20 100
Serious infection (%) 0.28 0.40
Hospital referral (%) 2.1 2.9
Immediate referral for serious
infection (%)
0.16 0.14
Delayed admission for serious
infections (%)
0.14 0.29

Results
• Antibiotic prescribing
– To be published

Conclusions
• Rule out level 5 mg/L in primary care
• Safe to restrict CRP to more seriously ill
children
• Better evidence on diagnostic value
– More impact?

Expanding Diagnostic Capacity - Multi-Disciplinary
Rapid Diagnostic and Assessment Centres
Dr Wai Lup Wong
Consultant Radiologist, East and North Hertfordshire
NHS Trust and Chair, Cancer Diagnostics CRG

Expanding Diagnostic Capacity:
Multidisciplinary Rapid Diagnostic and Assessment
Centres
Wai Lup Wong BA [Hons] LLM FRCR FRCP
Chair Cancer Diagnostics Clinical Reference Group NHS England

OVERVIEW
Consider the role of state of the art diagnostic imaging in the assessment of
people with cancer. In so doing highlight the limitations of advanced diagnostic
imaging. And demonstrate the requirement for [simple] blood tests to inform
cancer diagnostic pathways to improve care of people with cancer.
• Positron Emission Tomography CT [PET CT]
• Surveillance of people with treated prostate cancer
• Surveillance of people with treated head neck cancer
• Surveillance of carriers of faulty genes identified on genetic screening

There have been seismic advances in diagnostic imaging including for cancer,
paralleling advances in non imaging diagnostics over the past forty years
1970’s Usual investigations for
people with cancer
2017 Usual investigations for
people with cancer
• Refinements in existing technologies
Whole body MR , textural analysis
• PET MRI
Usual investigations for
people with cancer
EMERGING
• CT
• MR
• Ultrasound
• SPECT CT
• PET CT
• XR + contrast
• Bone scans

PET CT is a unique non-invasive imaging technique
PET CT shows information about metabolic cellular
activity with precise anatomical localisation
Cancers have abnormal metabolism and this can be detected by PET CT
Abnormal cellular activity proceeds morphological change in cancer
WHY IS PET CT A WINNING COMBINATION ?
PET CT is more accurate than usual imaging [US, CT, MRI] for detecting cancer

18F-FDG
the most common clinically used PET CT radiotracer localises
abnormal GLUCOSE metabolism
RADIOACTIVE MOLECULES USED WITH PET CT
18F-Choline
localises increased cell membrane turnover
68 Ga-PMSA
localises increased cell membrane turnover
18F-FACBC
localises abnormal amino acid uptake
FDG

PETCT
FDG ~
40 seconds 15-30 minutes

1 in 1000 of fatal cancer
1 in 5000 of non fatal cancer
1 in 4000 of inherited defect in off spring
One whole body FDG PET CT or
up to 8 years of natural radiation
detrimental effects: multiple by 2, in paediatric
patients; divide by 5, in 70+
years
ADDITIONAL LIFETIME RISK (16-69 year old)
Source: ARSAC 2006, HPA NRPB 2001, NCRP 1987

1 in 10
Very common
Common
Uncommon
1 in 100,000
Rare
Very rare
1 in 100
1 in 1000
1 in 10,000
3 balls in UK lottery
Death from smoking
10 cigarettes / day for 1 year
Death by RTA
4 balls in UK lottery
Death by murder
Death by accident at home
Death by accident at work
FAMILIAR RISKS
Death from fatal cancer (16-69 years old)
Death from fatal cancer (70+ years)
Death from fatal cancer (<16 years old)
Inherited defect in off spring

Men with Recurrent Prostate Cancer but not Detected on Usual Assessment
New cases of prostate cancer
2014, UK
2nd most common cancer in the UK

Recurrent Prostate Cancer : the Clinical Context
• Prostate cancer can recur in up to one in three men who have undergone treatment
with curative intent for localised disease .
Source: Cancer Research UK. If prostate cancer comes back. 2014
• Recurrence is initially demonstrated by a rise in total serum PSA often despite normal
findings with conventional imaging: biochemical relapse / recurrence
• Precise localisation of the site of recurrence is critical and provides a basis for further
therapeutic decisions.
• 16F-choline , 68Ga-PMSA , 16F-flucyclovine PETCT is potentially contributory.
Source: European Association of Urology. Guidelines on Prostate Cancer. 2015

available at
www.sciencedirect.com
journal homepage:
www.europeanurology.com
Collaborative Review – Prostate Cancer
New Clinical Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and a Promising
Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature
Laura Evangelista a,*, Alberto Briganti b, Stefano Fanti c, Stephen Joniau d, Sven Reske e, Riccardo Schiavina f, Christian Stief g, George N. Thalmann h, Maria Picchio i
E U R O P E A N U R O L O G Y 7 0 ( 2 0 1 6 ) 1 6 1 – 1 7 5
* bone scan
*
A: 5mm-7mm
B: 7mm-19mm
*
* Nodule @ primary site

E U R O P E A N U R O L O G Y 7 0 ( 2 0 1 6 ) 1 6 1 – 1 7 5
available at
www.sciencedirect.com
journal homepage:
www.europeanurology.com
Collaborative Review – Prostate Cancer
New Clinical Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and a Promising
Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature
Laura Evangelista a,*, Alberto Briganti b, Stefano Fanti c, Stephen Joniau d, Sven Reske e, Riccardo Schiavina f, Christian Stief g, George N. Thalmann h, Maria Picchio i
Choline 68Ga-PMSA
PSA <1ng/ml 20% (7-31) 49% (48-50)
PSA 1-2 ng/ml 46% (43-56) 68% (67-69)
PSA >2ng/ml 80% (72-81) 90%(88-92)
Detection rate by level of PSA Median (range)
Large, prospective, multicentre studies are necessary to evaluate the cost effectiveness, diagnostic
performance, impact on patient management and place in the patient care pathway of non-FDG tracers
(18F-FACBC or 68Ga-PSMA) in restaging of patients with suspected prostate cancer recurrence, including
consideration the place of non imaging diagnostics in pathways, established and emerging .

54 year old man with treated PROSTATE CANCER
High serum PSA [marker in the blood related relapse of prostate cancer
Investigations prior to PET CT including MR shows no disease
PET CT with F-CHOLINE shows the recurrent prostate cancer
not detected otherwise

People with Treated Head and Neck Cancer: Surveillance

In the Netherlands follow up offered to laryngeal cancer patients consists of 22 routine
visits over a time period of 10 years after treatment.
• Between 1990 and 1995 an asymptomatic cancer recurrence was found in only 2% of
the 402 patients who were treated with intention to cure , included 4639 visits
• There was no difference in survival and tumour mortality rates for patients with and
without symptoms.
CONCLUSIONS
Routine follow-up did not lead to survival beneﬁt for asymptomatic patients with tumour
recurrence.
Source: SC Ritoe, PFM Krabbe, JHAM Kaanders et al . Value of routine follow-up for patients cured of laryngeal
carcinoma. Cancer [2004] 1001:1382-9
The Value of Routine Follow-up in People Treated H&N Cancer is Unclear

Source: Fe De Felice, D Musio, V Tombolini Follow-up in H&N cancer: a management dilemma. Advances Otolaryngol 2015
There is lack of consensus as to the optimal follow-up of H&N cancer patients

Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in
head and neck cancer: a systematic review and meta-analysis
Conclusion
The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and
surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains
exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease.
European Journal of Nuclear Medicine and Molecular Imaging [2011] 38:2083
T Gupta, Z Master, S Kannan, JP Agarwal, S Ghsoh-Laskar, V Rangarajan V Murthy, A Budrukkar
A total of 51 studies involving 2,335 patients were included in the meta-analysis.
SENSITIVITY SPECIFICITY POSITIVE PREDICTIVE VALUE NEGATIVE PREDICTIVE
VALUE
PRIMARY SITE 79.9% (73.7–85.2%) 87.5% (85.2–89.5%) 58.6% (52.6–64.5%) 95.1% (93.5–96.5%)
NECK 72.7% (66.6–78.2%) 87.6% (85.7–89.3%) 52.1% (46.6–57.6%) 94.5% (93.1–95.7%)

N Engl J Med 2016;374:1444
OBJECTIVE
The main goal of the study was to determine if FDG PET-CT surveillance was not inferior to planned dissection.
METHOD
564 patients with advanced head and neck cancer [N2or N3] from 37 cancer treatment centres in the UK
Patients were randomly assigned to PET-CT surveillance or planned necked dissection.
The PET-CT group got chemoradiation and then PET-CT–surveillance (neck dissection was performed only if PET-CT showed
an incomplete or equivocal response to chemoradiation). Those in the second group got planned neck dissection.
Results
At a median follow up of 3 years, the PET-CT group had fewer neck dissections than those in the surgery group (54 versus
221 dissections, respectively).
The rate of surgical complications was similar in the two groups (42% versus 38%, respectively) as was quality of life and 2-
year overall survival rates [the surveillance group, 84.9%, the neck dissection group 81.5%].
PET-CT surveillance resulted in savings equivalent to about $2,200 U.S. dollars per patient over the course of the trial.

Tumour DNA as a biomarker for HNSCC. ctDNA
collected from patient plasma and saliva could
serve as a valuable marker of tumour burden to
monitor for response to treatment and disease
recurrence
…tumour DNA in saliva was found
post-surgically in three patients
before clinical diagnosis of
recurrence, but in none of the five
patients without recurrence........
Detection of somatic mutations and HPV in the saliva
and plasma of patients with head and neck squamous
cell carcinomas. Y Wang, S Springer, CL. Mulvey, N
Silliman, J Schaefer, M Saus et al. Science Translational
Medicine [2015] 7: 293:293

Stratification of people
treated head and neck cancer
Usual current assessment in an outpatient clinic
New ways of follow-up incl. H&N cancer markers
• Patient education
• Self reporting
• Blood tests
+ Improve patient experience
+ Improve outcomes
+ Improve value for tax payer
People with Treated Head and Neck Cancer: New Models for Surveillance
complex issues
Christies hospital , Manchester prostate cancer surveillance programme
*

Genomic Testing and Surveillance of healthy carriers of faulty genes: ……..

100,000 Genomes Project
To bring the predicted benefits of genomics to NHS patients is why the Prime
Minister launched the 100,000 Genomes Project in late 2012.
…. this flagship project which will sequence 100,000 whole genomes from NHS
patients by 2017.
Genomic testing: the UK context
36,083
OCT 31
2017

URGENT NEED FOR BLOOD TEST TO INFORM IMAGING DIAGNOSTICS
CHALLENGES associated with diagnostic imaging surveillance include:
• False NEGATIVE diagnostic scans
• False POSITIVE diagnostic scans
• Radiation exposure and risk of cancer
• Anxiety of having repeated scans and dealing with INDETERMINATE RESULTS
• Anxiety of having repeated scans and dealing with INCIDENTAL LESIONS
• OVERDIAGNOSIS- “malignant lesions that never surface in life”
The recent National Lung Cancer Screening trial did show a lower risk of dying from lung cancer in high-risk
individuals. Yet 40% of those who were screened were found to have abnormalities on screening that later
turned out to be benign.
Source: New England J Medicine [2011] 365:395
On the surveillance of healthy carriers of faulty genes

N Engl J Med 2016; 375:1483-1486
Editorial
Solving the Problem of Overdiagnosis
Joann G. Elmore, M.D., M.P.H.
Overdiagnosis of breast cancer with mammography screening….. overdiagnosis of thyroid cancer
accompanied the introduction of ultrasound screening,…. overdiagnosis of melanoma accompanied
widespread screening for skin cancer….. overdiagnosis of lung cancer associated with low-dose computed
tomographic screening examinations ….overdiagnosis of prostate cancer after prostate-specific antigen
testing have been reported
• Patient anxiety
• Unnecessary interventions
• Unnecessary morbidity
• Poor use of scarce resources ……..

“Absolute need for imaging and non imaging diagnosticians to
closely work together to develop diagnostic pathways where
blood tests inform imaging strategies, to improve the care of
people with cancer and make best use of scarce health resources
“
SUMMARY AND CONCLUSION

A Novel Biomarker for the Determination of Viral
Etiology in Febrile Illnesses
Dr Robert Sambursky
President & CTO/CMO, RPS

7878
Confidential and Proprietary to RPS
A Novel Biomarker for the Determination of
Viral Aetiology in Febrile Illnesses
Rob Sambursky, MD
President &
Chief Technology/Medical Officer
November 8, 2017

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Global Health Crisis Today
More than 20% of the global population seek care annually for
acute respiratory infection (ARI)1
80–90% of antibiotics are prescribed in general practice and 50%
for ARI2
Excessive use of antibiotics is the main cause of the increasing
antibiotic resistance2
60-80% of all patients consulting for cough, “cold” and sore
throat are prescribed an antibiotic3
Diagnostic uncertainty combined with patient pressures
influence physicians to prescribe antibiotics for more than 50%
of ARIs,despite a common viral aetiology4-5
[1] Gonzales R, Malone DC, Maselli JH, Sande MA. Clin Infect Dis 2001;33:757-62.[2] Goossens H, Ferech M, Vander SR, et al. Outpatient antibiotic use in Europe and association with resistance: a cross-
national database study. Lancet. 2005;365(9459):579–587. [3] Hawker JI, Smith S, Smith GE, et al. Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations
to reduce antibiotic resistance, UK 1995–2011 analysis of a large database of primary care consultations. J Antimicrob Chemother. 2014 [4] Ewig, S., and A. Torres. Severe community-acquired pneumonia.
Curr. Opin. Crit. Care. 2002; 8:453-460. [5] Little P, Stuart B, Francis N, et al. Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster,
randomised, factorial, controlled trial. Lancet. 2013;382(9899):1175–1182

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FebriDx: An Innovative Test for ARI
Rapid, point-of-care test that uses a fingerstick blood sample and the
body’s immune response to infections to help answer two key questions:
1. Is a clinically significant infection requiring treatment present?
2. Is it a viral or bacterial acute respiratory infection?
Detects an elevation of specific blood proteins
 Myxovirus resistance protein A (MxA) and C-reactive protein (CRP)
Hands-on procedure less than 2 minutes and positive results appear in as
soon as 10 minutes
Differentiates colonization from true systemic infection (unlike PCR, antigen
detection, and cell culture)
The Future
Today

8181
Current Pathogen Based Technologies
Available technology cannot support rapid triage of infectious patients or
support antibiotic stewardship in the outpatient setting
 Multiplexed protein arrays and molecular testing
 lack portability, rapidity and ease-of-use to provide immediate results
 Relatively more expensive and time consuming
 Selectively target multiple pathogens simultaneously but cannot broadly screen
against large numbers of possible infectious pathogens agnostically
 Cannot differentiate colonization from bonafide infection
 Antibody testing (e.g. Zika)
 Does not support initial screening
 IgM requires 5-7 days

8282
✓ Affordable – ~£12 single-use test
✓ Sensitive/Specific – Strong clinical data with a 97% NPV for bacterial infection
✓ User Friendly – Qualitative test; simple with minimal training required
✓ Rapid/Robust – Fingerstick with results within 10 minutes; 2 year shelf life/room temp
✓ Equipment Free – No electricity, batteries, or ancillary equipment
✓ Deliverable – Portable and disposable
The FebriDx ASSURED Solution

8383
Technology Utilizing Both MxA and CRP
[1] [1] Haller O, Freese M, Kpchs G. Rev Sci Tech 1998;17(1):220-30. [2] Nakabayashi M, Adachi Y, Itazawa T, et al. Pediatr Res 2006;60:770-774. [3] Kawamura M, Kusano A, Furuya A, et al. J Clin Lab Anal 2012;26:174-183. [4] Goetschy JF, Zeller H, Content J. J Virol
1989;63:2616-2622 [5] ] Falk G, Fahey T. Fam Prac 2009;26(1):10-21. [6] Andreola B, Bressan S, Callegaro S, et al. Ped Infect Dis J 2007;26(8):672-77. [7] Simon L, Gauvin F, Amre DK, et al. Clin Infec Dis 2004;39:206-17. [8] Salonen EM, Vaheri A. J Med Virol 1981;8(3):161-7. [9]
Halminen M, Ilonen J, Julkunen I, et al. Pediatr Res 1997;41:647-50.
MxA1-4 CRP5-9
Intracellular blood protein found in lymphocytes
which is stimulated by type I interferon
MxA levels remain low with bacterial infection
Sensitive and specific marker for viral infection
 Healthy people have a low concentration
[less than 15 ng/ml]2,3
 Fast induction after infection [1-2 hours]2
 Peaks at 16 hours and remains elevated in
the presence of elevated interferon4
 Long half-life [2.3 days]2
Acute-phase protein synthesized by the liver
Nonspecific marker for acute inflammation
At low levels, CRP is very sensitive but
nonspecific at confirming a bacterial infection
At high levels, CRP becomes very specific for
bacterial infection, but has low sensitivity
 Bacterial infection is a potent stimulus
 Elevates within 4-6 hours of infection and
peaks after 26 hours6-7
 Half-life is 18 hours6-7
Together, MxA and CRP provide an accurate way to differentiate
clinically significant viral from bacterial ARI
FebriDx®

8484
Kawamura et al1 (2012)
 Enrolled 60 patients
 31 confirmed viral infections (median MxA value 110.0 ng/ml)
 11 confirmed bacterial infections (median MxA value 10.6 ng/ml)
 Sensitivity of 87.1% and specificity of 90.9% for identifying viral infection
 Patients with viral infection were sharply distinguished from the healthy controls
with 100% sensitivity and specificity
Nakabayashi et al2 (2006)
 Enrolled 174 children
 122 with acute fever (respiratory infection and/or gastroenteritis)
 95 confirmed viral infections (mean MxA value 123.7 ng/ml ± 83.0 ng/ml)
 27 confirmed bacterial infections (mean MxA value 12.3 ng/ml ± 10.0 ng/ml)
 52 age-matched controls (mean MxA value 14.5 ng/ml ± 11.0 ng/ml)
 92.6% specificity and a positive likelihood ratio of 13.1 for accurately identifying
viral infection
[1] Kawamura M, Kusano A, Furuya A, et al. J Clin Lab Anal 2012;26:174-83. [2] Nakabayashi M, Adachi Y, Itazawa T, et al. Pediatr Res 2006;60:770-74. [*] Data corrected for recalibrated ELISA MxA standard of f 37.5 ng/ml
MxA Clinical Support Using ELISA

8585
Viral Biomarker Comparison
AUC for MxA was shown to be the following1:
 0.98 (95% CI: 0.96–1.0) for viral vs uninfected
 0.89 (95% CI: 0.82–0.96) for viral vs bacterial infection
AUC for TNF-related apoptosis inducing ligand (Trail) / IP-102
 0.72 (95% CI [0.56-88]) for TRAIL
 0.72 (95% CI 0.59-86) for IP-10
AUC for MxA (0.77) versus TRAIL (0.66) for pharyngitis3
[1] Engelmann I1, Dubos F1, Lobert PE1, Houssin C et al. Diagnosis of viral infections using myxovirus resistance protein A (MxA). Pediatrics. 2015 Apr;135(4):e985-93. [2] van der Does Y, Tjikhoeri A, Ramakers C, Rood PP, van Gorp EC, Limper M. TRAIL and IP-
10 as biomarkers of viral infections in the emergency department. J Infect. 2016 Jun;72(6):761-33] Ivaska L, Niemelä J, Lempainen J, Österback R et al. Aetiology of febrile pharyngitis in children: Potential of myxovirus resistance protein A (MxA) as a biomarker of viral
infection. J Infect. 2017 Apr;74(4):385-392.
Receiver Operating Characteristic curve for myxovirus resistance
protein A to detect patients without group A streptococcus
among children with febrile pharyngitis (n=83) - AUC was 0.773.
Receiver Operating Characteristic curve for TNF-related apoptosis-
inducing ligand to detect patients without group A streptococcus
among children with febrile pharyngitis (n=83) - AUC was 0.657.
Viral vs Uninfected Viral vs Bacterial

8686
CRP Outcome Studies
A multicentre trial in six European countries using CRP or communication training led to a
marked reduction in antibiotic prescribing for ARI in primary care1
A Cochrane review with CRP cut-off of 20 mg/L significantly reduced antibiotic use without
increased morbidity2
 36.2% (37.6% vs 58.9%) in patients presenting with acute cough or LRTI (bronchitis, pneumonia, COPD
exacerbation, and asthma)
 31.3% (33% vs 48%) URI
 24.4% (59 vs 78%) in sinusitis
 23.3% (43.4% vs 56.6%) in rhinosinusitis
NICE Guidelines support CRP at 20 mg/L as a threshold to capture serious bacterial infection
 Normal range < 5mg/L and controlled rheumatic disease < 10 mg/L3
 Elevated CRP levels ≥ 20 mg/L indicate a potentially clinically significant infection is present but cannot
differentiate viral from bacterial infection due to low specificity4
 Influenza A/B, Parainfluenza, Adenovirus, EBV, HSV, VZV significant CRP elevation ≥ 20 mg/L
 Testing with CRP alone may lead to unnecessary antibiotic prescriptions for patients with a viral infection3 of more
than 38% of patients with ARI3,5
 Reduces the risk of missing a clinically significant infection
[1] Little P, Stuart B, Francis N, et al. Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled
trial. Lancet. 2013;382(9899):1175–1182.[2] Cooke J, Butler C, Hopstaken R, et al. BMJ Open Respir Res. 2015 May 6;2(1):e000086. [3] Self W et al. Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune
Responses to Viral and Bacterial Upper Respiratory Infections. Journal of Clinical Medicine. 2017, submitted. [4] Point-of-care test (POCT) for C-reactive protein (CRP). Department of Primary Health Diagnostic Horizon
Scanning Centre, Horizon Report 0017, July 2011.[5] Salonen EM, Vaheri A. C-reactive protein in acute viral infections. J Med Virol 1981;8(3):161-7

8787
CRP + MxA Receiver Operator Curve
A MULTIPLEXED PATTERN OF RESULTS
Combining an MxA value with CRP provides an accurate
way to differentiate clinically significant viral from
bacterial acute respiratory infection.
In isolation, neither MxA nor CRP
independently is sensitive or
specific enough to differentiate viral
from bacterial infection
 At low levels, CRP is very sensitive but
nonspecific at confirming a bacterial
infection
 At high levels, CRP becomes very specific
for a bacterial infection but has low
sensitivity
 MxA is specific to identify viral infection
only and is insensitive for the presence
of bacterial infection

8888
[1] Engelmann I, Dubos F, Lobert PE, et al. Pediatrics 2015;135:e985-93.
Prospective clinical study examined 553 children consisting of 44
uninfected controls and 77 confirmed viral infections and found:
A combination of MxA ELISA and CRP ELISA testing for differentiating viral
from bacterial infection and determined:
 The ROC curve: 0.84
 95% CI: 0.75-0.94
 Sensitivity: 80.9%
 95% CI: 66.7-90.8
 Specificity: 87.9%
 95% CI: 71.8-96.5
Combined CRP + MxA Clinical Support

8989
Strong Clinical Performance Results
N = 370 patients enrolled through U.S. multicentre clinical evaluation of FebriDx
at major academic centers – Patients with reported fever within 72 hours and
respiratory tract symptoms/signs
 165 asymptomatic patients - less than 1% false positive results
 205 URI patients [inclusive of acute bronchitis]
 38% confirmed infectious by gold standard reference tests
• 12% Bacterial
• 26% Viral
 62% Microbiologically Unconfirmed Respiratory Illness (MURI)
97% NPV for bacterial
infection improves antibiotic
stewardship
Encourages delayed
prescribing antibiotic strategy
Reference Tests
Viral testing
 BioFire respiratory PCR panel
 Influenza A/B, Adenovirus, RSV,
Parainfluenza, Metapneumovirus
 Rhinovirus and Coronavirus
associated with elevated MxA ELISA
 Additional PCR testing for HSV and CMV
 Serum Epstein-Barr IgM/IgG
Bacterial testing
 Chlamydia pneumoniae,
mycoplasma pneumoniae,
Bordetella pertussis
 Throat culture
Laboratory testing
 Procalcitonin
 White blood cell count (WBC)
95% CI (Wilson score)
Performance Value P(%) Ratio Lower Upper p - Value
Sensitivity Bacterial (% Positive Agreement) 80% 20/25 60.80% 91.10% 0.048
Specificity Bacterial (% Negative Agreement) 93% 168/180 89.40% 96.60% 0.0410
PPV Bacterial 62% 20/32 47.00% 78.90% 0.053*
NPV Bacterial 97% 168/173 93.50% 98.80% 0.0009
Group A/C Beta Hemolytic Streptococcus 90% 9/10 59.60% 98.20% 0.0434
Sensitivity Viral (% Positive Agreement) 86% 56/65 75.10% 93.50% 0.0237
Specificity Viral (% Negative Agreement) 88% 124/140 76.10% 88.10% 0.0123
PPV Viral 78% 56/72 52.40% 74.00% 0.0092
NPV Viral 93% 124/133 89.50% 97.40% 0.0343
Influenza A/B 89% 31/34 74.10% 95.50% 0.0319
FebriDx is regulatory cleared in Europe and Canada.
FebriDx is not FDA cleared and is not available in the United States.
Self W et al. Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral
and BacterialUpper Respiratory Infections. Journal of Clinical Medicine. 2017, submitted.

9090
…Strong Clinical Performance
Major inclusion criteria for study 2 included: age > 1 year, new fever ≥
100.5ºF exhibited within the past 3 days, and new onset of cough or sore
throat within the past 7 days
Major exclusion criteria included use of antibiotics, antiviral agents,
interferon therapy, immunosuppressive therapy or a live viral immunization
within the past 30 days
N=112
 Bacterial Infection:
 Positive Agreement = 94% (17/18)
 Negative Agreement = 94% (88/94)
 Viral Infection:
 Positive Agreement = 90% (72/80)
 Negative Agreement = 85% (29/34)
Reference Tests
Viral testing
 Influenza A/B, Adenovirus, RSV,
Parainfluenza, Metapneumovirus
 Rhinovirus and Coronavirus associated
with elevated MxA ELISA
 Additional PCR testing for HSV and CMV
 Serum Epstein-Barr IgM/IgG
Bacterial testing
 Chlamydia pneumoniae, mycoplasma
pneumoniae, Bordetella pertussis
 PCR for Fusobacterium and Neisseria
 Throat culture
Laboratory testing
 Procalcitonin
 White blood cell count (WBC)

9191
UK Outcome Study 2017 Results
Introduction
 A retrospective chart review was performed on 21 patients that presented to an outpatient general practice with
symptoms of an acute respiratory tract infection and were administered the FebriDx test
Results
 Mean age of 46.3 years, ranging in age from 3 years to 84 years old
 Clinical diagnoses of nonspecific upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI)
 FebriDx altered clinical management in 48% (10/21) and reduced unnecessary antibiotic prescriptions in 80% (8/10)
 All of the patients demonstrated full clinical recovery without additional unscheduled medical consultations or
subsequent newly initiated antibiotic prescriptions
Conclusion
 Point-of-Care (POC) diagnostic testing may help primary care general practitioners cost-effectively manage patients
presenting with clinical evidence of an acute febrile respiratory tract infection
 FebriDx test results improved clinical management decisions and resulted in a reduction in antibiotic therapy without
any subsequent adverse events
Davidson M (2017) FebriDx Point-of-Care Testing to Guide Antibiotic Therapy for Acute Respiratory Tract Infection in UK Primary Care: A Retrospective Outcome Analysis. J Infect Dis Preve Med 5: 165.

9292
FebriDx versus CRP
Viral infections frequently
increase CRP ≥ 20 mg/l:
 Influenza A/B1-3,
 Adenovirus1-2,5-6
 Epstein-Barr6
 Parainfluenza2
 Cytomegalovirus1,4
 Herpes simplex1,4
 Varicella-Zoster1,4
[1] Salonen EM, Vaheri A. C-reactive protein in acute viral infections. J Med Virol 1981;8(3):161-7. [2] Melbye H, Hvidsten D, Holm A, Nordbø SA, Brox J. The course of C-reactive protein response in untreated upper respiratory tract
infection. The British Journal of General Practice. 2004;54(506):653-658. [3] Whicher JT, Chambers RE, Higginson J, et al. Acute phase response of serum amyloid A protein and C reactive protein to the common cold and influenza. J
Clin Pathol. 1985;8: 312–316. [4] Sarov I, Shainkin-Kestenbaum R, Zimlichman R, et al. Serum amyloid A levels in patients with infections due to cytomegalovirus, varicella-zoster virus and Herpes simplex virus. J Infect Dis
1982;146:443.. [5] Halminen M, Ilonen J, Julkunen I, et al. Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children. Pediatr Res. 1997; 41:647-650. [6] Putto, A.,
Meurman, O. & Ruuskanen, O. C-reactive protein in the differentiation of adenoviral, Epstein-Barr viral and streptococcal tonsillitis in children.Eur J Pediatr (1986) 145: 204.
FebriDx® accurately
identified (18/24)
Received unnecessary
antibiotics
Use of the FebriDx test would reduce the over prescription of
antibiotics in 75% (18/24) of confirmed cases of viral infection
compared with using CRP independently2
Viral infection (N=58)
(PCR confirmation)
URI patients (N=205)1
Viral infection (34/58)
MxA ≥ 40 ng/ml
CRP < 20 mg/L
Viral infection (22/58)
MxA ≥ 40 ng/ml
CRP ≥ 20 mg/L
38% of viral infections showed CRP ≥ 20 mg/L
[1] Self WH, Rosen J, Sharp SC, et al. Diagnostic accuracy of FebriDx: A rapid test to detect immune responses to viral and
bacterial upper respiratory infections. J Clin Med. 2017;6(10):E94 [2] Sambursky R, Shapiro N. FebriDx: the ability of a 10-
minute rapid point-of-care immunoassay to reduce antibiotic prescriptions for acute febrile respiratory infection. Poster
presented at: European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2015. Copenhagen, Denmark.

9393
[1] Huddy JR, Ni MZ, Barlow J, et al Point-of-care C reactive protein for the diagnosis of lower respiratory tract infection in NHS primary care: a qualitative study of barriers and facilitators to adoption BMJ Open 2016;6:e009959.[2]
Davidson M (2017) FebriDx Point-of-Care Testing to Guide Antibiotic Therapy for Acute Respiratory Tract Infection in UK Primary Care: A Retrospective Outcome Analysis. J Infect Dis Preve Med 5: 165.
Workflow and Antibiotic Reduction
Unscheduled Patients1
History of fever and respiratory symptoms
FebriDx performed by
staff
FebriDx performed by
GP
GP sees next patient to
increase efficiency
FebriDx guides clinical management
and therapeutic decisions
FebriDx confirms viral
infection or MURI –
no antibiotics
FebriDx confirms
bacterial infection –
antibiotics given
Less antibiotic use, less antibiotic
complications, less unscheduled consultations,
and less costs
Positive results develop in less than
10 minutes and negative results in less
than 15 minutes
1 minute to perform test
48% of clinical management decisions altered2
80% reduction in unnecessary scripts2

9494
FebriDx Impact – United Kingdom
[1] United States Census Bureau – United Kingdom: http://www.census.gov/popclock/world/uk. [2] World Health Organization – Europe. Data and statistics: http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/data-and-statistics. [3]
Acute respiratory infections: the forgotten pandemic. Bulletin of the World Health Organization. 1998;76(1):101-107. [4] Rattinger GB, Mullins CD, Zuckerman IH, et al. A sustainable strategy to prevent misuse of antibiotics for acute respiratory infections. PLoS
One 2012;7(12):e51147. [5] Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis 2008;47(6):735-43.
UK 5-year Antimicrobial Resistance Strategy
 Conserve and steward the effectiveness of
existing treatments
 Unnecessary antibiotic prescriptions lead
to antibiotic resistance, antibiotic allergies
and toxicities, resulting in adverse events
and higher costs

9595
7227 Delainey Court
Sarasota, FL 34202
941-556-1850
rpsdetectors.com
THANK YOU!

Workshop 2 - Antibiotic Resistance - Reducing
Prescribing Through POC Rapid Diagnostics
Implementing Recommendation 5 from the
Review on Antimicrobial Resistance:
Jonathan Cooke Imperial College London and
University of Manchester
j.cooke@imperial.ac.uk
jonathan.cooke@manchester.ac.uk

Treatment of RTI in Primary Care
• Most RTIs are viral
• Evidence from systematic reviews
(Smith et al 2004) and other studies
(Butler et al 2009; Little et al 2013)
suggest only slight benefit is
achieved from the prescription of
antibiotics

The Cochrane Library November 2014, Issue 11
CRP POCT: Does it work?

Guidelines that include CRP POCT
• NICE PNEUMONIA CLINICAL GUIDELINE 191:
Pneumonia: diagnosis and management of
community-and hospital-acquired pneumonia in
adults 2014
• Public Health England PHE - Managing common
infections: guidance for primary care - 2017
• The European Respiratory Society’s guidelines for the
management of LTRIs in adults recommend CRP
testing in patients with suspected pneumonia - 2011

• Megraj room, 1st floor, Commonwealth
Building, Hammersmith Campus, W12
0NN

• Megraj room, 1st floor, Commonwealth
Building, Hammersmith Campus, W12
0NN
CRP POCT wide extent
CRP POCT some extent

Conclusion
• AMR is a serious global issue
• Too many unnecessary prescriptions for
antibiotics are written in primary care
• CRP POCT offers precision in the diagnosis
and management of RTIs in primary care
• CRP POCT is cost-effective
• Reduction in primary care antibiotic
prescriptions contribute to reducing the UK’s
AMR strategy

Workshop 4-The “NICE” Challenge of
Early Onset Neonatal Sepsis and the
later problems
Elizabeth Pilling
Consultant Neonatologist
Jessop Wing, Sheffield

Introduction
• 2014- UK Prime Minister commissioned review on
antimicrobial resistance
• 2016- final report published- supported by Wellcome
trust and UK government- the O’Neill report
• 2 key aims with 9 interventions
– We must increase the supply of new antimicrobials
effective against drug resistance bugs
– We must reduce the demand for antimicrobials so the
current stock of drugs lasts longer

We must reduce the demand for
antimicrobials so the current stock of
drugs lasts longer
• INTERVENTION 1
– A global public health campaign
• INTERVENTION 2
– Improve sanitation and prevent the spread of infection
• INTERVENTION 3
– Reduce unnecessary use of antimicrobials in agriculture and their dissemination into the environment
• INTERVENTION 4
– Improve global surveillance of drug resistance and antimicrobial consumption in humans and animals
• INTERVENTION 5
– Promote new, rapid diagnostics to reduce unnecessary use of antimicrobials
• INTERVENTION 6
– Promote development and use of vaccines and alternatives
• INTERVENTION 7
– Improve the number, pay and recognition of people working in infectious disease

We must increase the supply of new
antimicrobials effective against drug
resistance bugs• INTERVENTION 8
– A global innovation fund for early stage and non-commercial R&D
• INTERVENTION 9
– Better incentives to promote investment for new drugs and improving existing ones

Introduction
• Neonatology
– Children <28 days
• 2 populations
– “well” infants with their mothers on post-natal
wards
– Unwell or preterm infants cared for on neonatal
unit
• Intensive care
• High dependency care
• Special care

Introduction
• High level of antibiotic usage
• On postnatal ward
– contributes to length of stay of both mother and
baby
• On neonatal unit
– issues of antimicrobial stewardship
– High levels of broad spectrum exposure
– Long stays (6 months)

Background
• Early onset sepsis <72 hours of age
• Pathogenic organisms
– Group B strep, E Coli, Haemophilus influenza, listeria
• NICE Neonatal infection (early onset): antibiotics for
prevention and treatment (CG 149) published August 20121
• Indications for starting antibiotics
– 1 red flag
– 2 risk factors/clinical indicators
• Predominantly applied to well infants who remain with their
mothers on the post natal wards

Red Flags
Parenteral antibiotics given to the mother for
confirmed or suspected invasive bacterial infection
Suspected or confirmed infection in another baby
where there is a multiple pregnancy
Respiratory distress starting more than 4 h after birth
Seizures
Need for mechanical ventilation in a term baby
Signs of shock

Risk Factors
• Invasive group B streptococcal infection in a previous baby
• Maternal group B streptococcal colonisation, bacteriuria or
infection in the current pregnancy
• Prelabour rupture of membranes
• Preterm birth following spontaneous labour (before 37
weeks' gestation)
• Suspected or confirmed rupture of membranes for more
than 18 hours in a preterm birth, 24 for term
• Intrapartum fever higher than 38°C, or confirmed or
suspected chorioamnionitis

Clinical Indicators
• Altered behaviour or responsiveness
• Altered muscle tone (for example, floppiness)
• Feeding difficulties (for example, feed refusal)
• Feed intolerance, including vomiting, excessive gastric aspirates and abdominal distension
• Abnormal heart rate (bradycardia or tachycardia)
• Signs of respiratory distress
• Hypoxia (for example, central cyanosis or reduced oxygen saturation level)
• Jaundice within 24 hours of birth
• Apnoea
• Signs of neonatal encephalopathy
• Need for cardio–pulmonary resuscitation
• Need for mechanical ventilation in a preterm baby
• Persistent fetal circulation (persistent pulmonary hypertension)
• Temperature abnormality (lower than 36°C or higher than 38°C) unexplained by environmental
factors
• Unexplained excessive bleeding, thrombocytopenia, or abnormal coagulation (International
Normalised Ratio greater than 2.0)
• Oliguria persisting beyond 24 hours after birth
• Altered glucose homeostasis (hypoglycaemia or hyperglycaemia
• Metabolic acidosis (base deficit of 10 mmol/litre or greater)
• Local signs of infection (for example, affecting the skin or eye)

Investigations/Treatment
• Investigations
– Blood culture
– FBC
– CRP, repeated at 18-24 hours
• Benzyl penicillin/gentamicin
• Consider stopping antibiotics if ALL
– Cultures negative at 36 hours
– CRPs both <10
– Baby well
• LP if CRP >10 or positive culture/signs of meningitis
• 7/7 antibiotics if CRP>10

Hopes
• Reduced length of stay with 36 hour blood
cultures
• Reduced antibiotic use
• Predicted £50 million/year cost saving

Challenges
• What is “suspected maternal invasive bacterial
infection” and who defines it?
• Increased work load (2nd CRP)
• CRP of 10 to rule in and out infection
• Increased lumbar punctures
• Getting blood culture results at 36 hours
• What to do about 2nd dose of gentamicin/levels

Case 1-Emily
• 39/40 gestation, 3rd baby
• Normal pregnancy and
delivery
• Membranes ruptured 12
hours before delivery
• Born 1800 1/1/17
• At 1830, maternal pyrexia
• IV antibiotics given to
mother

Emily
• Neonatal team called
• Normal examination
• Investigations performed
• Antibiotics commenced
1930
• Mum well and keen for “6
hour discharge”

Emily
• Blood cultures reach lab
2230
• Incubated from 0100 2/1
• Repeat CRP 2/1 1200
• Both CRPs <10
• Cultures negative at 36 hours
1300 3/1
• Paediatric team reviewed
1430
• Discharged home 1530 3/1-
45 ½ hour stay

Is the NICE guideline being followed?2
• Telephone survey of tertiary neonatal intensive
care units
• 56 of 59 responded

Compliance with NICE recommendations.
Arindam Mukherjee et al. Arch Dis Child Fetal Neonatal Ed
2015;100:F185
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

Sheffield experience
• New guideline implemented 2013
• Differed CRP guidance
– <10x2 and well can discharge
– >40 suggest LP and minimum 5/7 antibiotics
– CRP 10-40, depends on indications for initial investigations,
clinical findings and blood culture results
• Feeling that increased antibiotic usage and increased
length of stay
• Problem with shortage of postnatal ward beds

Other local challenges
• Microbiology lab 4 miles from maternity unit
• Samples transported at set times
• Over night no routine incubating of blood cultures
• Mean 5 hours 36 mins from sampling to
incubating blood cultures
• Reluctance to discharge newborn infants out of
hours-again limits discharge at 36 hours at night

Sheffield audit-Feb/March 2016
• 117 infants tested
• 1.95 infants per day (10% of births)
• 24 “unwell” admitted to NNU/preterm infants
• 3 clinical notes could not be found
• 90 “well” postnatal ward infants reviewed

Results
• Reasons for starting antibiotics:
– Red flags
• 54% suspected maternal sepsis
• 2% co-twin treated for suspected sepsis
– Risk factors
• 39% maternal GBS colonisation
• 32% prolonged rupture of membranes
• 12% preterm labour
• 6% suspected chorioamnionitis
• 1% previous infant with GBS
– Clinical indicators
• 9% signs of respiratory distress
• 2% poor apgars
• 2% temperature instability

Results
• No positive blood cultures found
• 12 infants (13%) received 5/7 antibiotics due to
clinical concerns/increased CRP

Length of stay
• For whole tested group
– Mean 3.11 days
• Range 2-9 days
• Of those fit for discharge pending blood
cultures
• 60 babies
– mean 2.30 days
• Range 2-5 days

Impact
• Cost
– Maternal bed
– Antibiotics
– Nursing time
• Family impact
– Family separation
• Risks
– Antibiotic exposure/microbiome long term effects
– Gentamicin side effects

NICU patients
• Late onset sepsis for
infants receiving neonatal
intensive care
– Incidence of sepsis 22-45%
for infants <1500g
– Usage of antibiotics higher

How big is the problem?
• Cause of death data-EPICure 1 (1995)7 and EPICure 2 (2006)8
• Infants 22-26/40 gestation
• Infection as cause of death increasing
EPICure %
n=400
EPICure 2 %
n=522
% difference
Congenital malformation 2 1 -1
Pulmonary insufficiency 30 16 -13
RDS/ICH/Infection 31 33 +2
Late sequelae of ventilation 9 8 -2
Infection 8 16 +8
NEC 3 12 +9

Case 2- Daisy
• Born at 25 weeks
gestation
• 613g (1lb5oz)
• Admitted for 158
days

• Long line for 30 days
• 4 long line infections
• 10x “courses” of antibiotics
• All culture negative
• Some continued for 5-7
days
• 72 days of antibiotics

Other problems
• Fungal sepsis significant complication
• Resistance concerns
– MRSA
– VRE
– CPE
• Increased risk of necrotising enterocolitis 6
• After 1 to 2 days of antibiotic exposure risk increased by 1.19 times
• 1.43 for 3 to 4 days
• 2.45 for 9 to 10 days
• 2.94 for >10 days of exposure
• Neonatal microbiome changed for up to 5 years
– Increased risk of death, length of stay, NEC, candida, resistance, asthma

A possible option for early “rule-out”
• Cognitor minus
– Gives a “negative” blood culture after 12 hours
– Detects bacteria/fungal DNA polymerase
– 99.5% NPV (mostly adult samples)
• “Behind the scenes” evaluation
• 117 infants

Results
• No positive blood cultures found
• 88.9% (80) “negative”
• 8.9% (8) “not determined”
• 2.2% (2) unresolved

Length of stay
• For whole tested group
• Mean 3.11 days
– Range 2-9 days
• With Cognitor Minus “negative”
• Result available mean 10 hours earlier than culture
• 2.46 days
– Range 1-9 days

Of those fit for discharge pending
blood cultures
– 60 babies
• mean 2.30 days
– Range 2-5 days
• With Cognitor minus “negative”
• Mean 1.28 days
– Range 1-3

Economic evaluation
• 58.8% (53) fit for discharge 1 night earlier
• Some not ready for discharge for other reasons (jaundice,
maternal illness, other investigations, time of day)
• Not included
– Nursing time for antibiotic administration
– Cannulation time
– Drugs
– Disposables
– Gentamicin levels
– Lab time to undertake test

Economic evaluation
• Cost saving
– Cost of postnatal ward bed
– Cost of Cognitor Minus test for all babies (700/year)
+ income for infant
• 319 bed nights/year
• £47000 per year

Current status
• Automation in progress
• “not determined” to give more detail
– Positive
– Gram +ve/-ve/fungus
• Further evaluation for neonatal samples
– positive blood cultures
• Still have some antibiotic exposure

Summary
• We desperately need a way of diagnosing sepsis
– Ruling in
• Identifying organism
• Allowing appropriate treatment
– Ruling out
• In mothers
– To prevent the need to start antibiotics on the baby (in addition to
their own heath)
• In babies
– To reduce antibiotic exposure
– To get them home

References
1. NICE guidelines CG149. Neonatal infection (early onset): antibiotics for prevention and treatment. August 2012.
2. Management of neonatal early onset sepsis (CG149): compliance of neonatal units in the UK with NICE
recommendations. Arch Dis Child Fetal Neonatal Ed 2015;100:F185. Arindam Mukherjee1, Babu Ramalingaiah1, Nigel
Kennea2, Donovan Alistair Duffy2
3. Implementation of the NICE prevention and treatment of early onset neonatal infection guideline: the Glasgow
experience. Arch Dis Child Fetal Neonatal Ed 2017;102:F91-F92 doi:10.1136/archdischild-2016-310856 Letter. Jennifer
Mitchell1, Sandy Kirolos2, Lesley Jackson2, Andrew Powls3
4. NICE neonatal early onset sepsis guidance: greater consistency, but more investigations, and greater length of stay. Arch
Dis Child Fetal Neonatal Ed 2015;100:F248-F249 doi:10.1136/archdischild-2014-306349. Arindam Mukherjee, Louise
Davidson, Lazarus Anguvaa, Donovan, Alistair Duffy,Nigel Kennea
5. Blood culture volume and detection of coagulase negative staphylococcal septicaemia in neonates. Arch Dis Child Fetal
Neonatal Ed. 1997 Jan;76(1):F57-8. Jawaheer G1, Neal TJ, Shaw NJ.
6. Antibiotic Exposure in the Newborn Intensive Care Unit and the Risk of Necrotizing Enterocolitis . The Journal of
Pediatrics, Volume 159, Issue 3, September 2011, Pages 392–397. Vanaja N. Alexander, MDa, Veronika
Northrup, MPHb, Matthew J. Bizzarro, MDa, ,
7. The EPICure Study: Outcomes to Discharge From Hospital for Infants Born at the Threshold of Viability. Pediatrics,
October 2000, VOLUME 106 / ISSUE 4. Kate Costeloe, Enid Hennessy, Alan T. Gibson, Neil Marlow, Andrew R. Wilkinson,
for the EPICure Study Group
8. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure
studies. BMJ 2012; 345:e7961 doi. Moore T., Hennessy E.M., Myles J., Johnson S.J., Draper E.S., Costeloe K.L., Marlow N.
9. TACKLING DRUG-RESISTANTINFECTIONS GLOBALLY: FINAL REPORT AND RECOMMENDATIONS THE REVIEW
ANTIMICROBIAL RESISTANCE CHAIRED BY JIM O’NEILL MAY 2016 https://amr-
review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf

Roundtable - To fund or not to fund, this is the question
Rosanna W Peeling, Professor and Chair, Diagnostic Research Director, International
Diagnostics Centre London School of Hygiene & Tropical Medicine
Doris-Ann Williams, Chief Executive, BIVDA
Dr Elisabeth Adams, Managing Director, Aquarius Population Health Limited
Dr Vicki Chalker, Head, Respiratory and Vaccine Preventable Bacteria Reference Unit,
National Infection Service, Public Health England
Tweet Questions using- #UKDiagnosticsPanel

Diagnostics in action- Providing access to personalised
medicine by improving diagnostic strategies
Dr Michael Hubank
Head of Clinical Genomics (Research), The Royal
Marsden Hospital

Care pathway modelling
Case Study
Mologic Headstart COPD Exacerbation test
Diagnostic Evidence Co-operative Newcastle
Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University
Sara Graziadio and Michael Power
UK Diagnostics Summit
8 November 2017

Agenda
• Introductions
– You to us
– Us to you
– Aims: Yours (???) and Ours (Interactive and Adaptive)
• Care Pathway Modelling
– What do you (need to) know about care pathways?
– What is a care pathway?
– Why is it useful?
– How to map a care pathway?
– What is care pathway modelling?
– When would you need to map or model a care pathway?
• Wrap up

The NIHR Diagnostic Evidence
Cooperative (DEC) Newcastle
Funded by:
• The National Institute for Health
Research
Partnership between:
• NuTH
• Newcastle University
Facilitates evidence on:
- Clinical validity
- Clinical utility
- Value for money
- Affordability
of in vitro diagnostic medical devices
(IVDs) for use in the NHS

NIHR Medtech and In vitro diagnostic
Co-operatives (MICs) from January 2018.
Leading NHS organisations have been awarded funding to host NIHR MICs.
Over £14 million has been awarded across 11 NIHR MICs!
Newcastle IVD Co-operative:
Clinical themes:
• Aging – Led by Dr James Frith
• Precision Medicine - Led by Professor Nick Reynolds
• Infection – Led by Dr Ashley Price
Methodological themes:
• Early decision and economic modelling
• Clinical decision aid development
• Imperfect reference standard methodology development

Agenda
• Introductions
– You to us
– Us to you
– Aims
• Wrap up

Care pathway analysis
What?
• Map current pathways
o Who?
o Decisions/Alternatives?
o Paths
o Processes with:
▻Activities
▻Resources
▻Costs/utilities
o Outcomes
▻∑costs
▻∑utilities
• Potential changes to current
pathways
Outcomes: clinical, resources, costs?

Agenda
• Introductions
– You to us
– Us to you
– Aims
• Wrap up

Care pathway analysis
Why?
• Helps you to identify:
o The base case for
comparison
o Opportunities for
improvement from
adopting the product
o Outcome measures to
assess improvement from
adopting the product
o Potential barriers to
adoption
o Design clinical studies
What?
• Map current pathways
o Who?
o Decisions/Alternatives?
o Paths
o Processes with:
▻Activities
▻Resources
▻Costs/utilities
o Outcomes
▻∑costs
▻∑utilities
• Potential changes to current
pathways

Agenda
• Introductions
– You to us
– Us to you
– Aims
– What do you (need to) know about care pathway modelling?
• Wrap up

Mologic Ltd – Headstart test for
exacerbation of COPD –Innovate UK
HOW?
• Literature review
(guidelines, HTAs)
• Engage stakeholders
• Focus groups
• Surveys
• …

Care pathway model
Structure
Root
Path
Node
Outcomes
Parameters
Probabilities
Resource usage
Costs/Utilities
--------
£££££/Utils
=====
Base case
New pathway
Computational model

• Patient benefits
• Patient harms
• Sensitivity
• Specificity
• Predictive values
• Accuracy
• Reproducibility
• Safety
IVD developers
 Academia
 Industry
 NHS
Stakeholders
 Patients
 Commissioners
 Healthcare professionals
 Clinical networks
Analytic
validity
Diagnostic
accuracy Clinical utility
Actual value:
Business case development
• Patient outcomes
• Economic value
• Budget impact
• Feasibility of
implementation
Discovery or Invention
Clinical
performance
R&D laboratory
performance
Demonstration of patient
outcomes
Early economic modelling
Value of information analysis
Care pathway analysis and process modelling
Adoption & implementation
Adopters
▪ System (DH)
▪ NHS Commissioners
▪ NHS Providers
HealthEconomic
Studies
Stakeholder
engagement
Early assessment of
potential value
Barriers and facilitators to adoption
Usability and human factors
Full economic assessment
PrototypeCE marking Final product
Evidence development pathway
to support adoption of an IVD by the NHS
Headroom analysis

Contact us
Email: ray.waters@ncl.ac.uk, stephen.lynn@nuth.nhs.uk
Ray Waters (Project Manager) Dr Stephen Lynn (Industry Liaison lead)
Website: www.newcastle.dec.nihr.ac.uk
@NIHR_DEC_Ncl
Joy.Allen@ncl.ac.uk, Sara.Graziadio@ncl.ac.uk, Will.Jones@ncl.ac.uk
Michael.Power@ncl.ac.uk

Diagnostics in action - The Emergency Multidisciplinary
Unit (EMU)
Dr Daniel Lasserson
GP and Professor of Ambulatory Care, Institute of
Applied Health Research, College of Medical and
Dental Sciences, University of Birmingham

Diagnostics in Action
The Emergency Multidisciplinary
Unit
Dan Lasserson MA MD FRCP Edin MRCGP
Professor of Ambulatory Care
@DanLasserson

What is ambulatory emergency care?
• Diagnosis, observation, treatment, rehabilitation not
provided in the traditional hospital bed base or out-
patients
• Needs observation periods, rapid diagnostics, decision-
makers, reassessments
• “Improved patient experience…reduce negative impact
of hospital admission…cost-effective..”

Ambulatory emergency care outside hospital
• Accessible, rapidly responding, multidisciplinary
diagnosis and treatment from a community setting
• Credible alternative to acute hospital admission
• Personalised acute care process, tailored to risk, patient
and carer preference
• Platform for innovation in care models for older patients
living with frailty – allowing an organisation to learn

Disruptive innovation in the existing
acute care pathway
• Hospitalists working outside the ‘hospital walls’ for acute – what do
they take with them?
• Evolving a new kind of community physician at the interface of
primary and secondary care
• Taking the learning back into an acute hospital
• What improves patient and carer experience of acute assessment
and treatment?

A journey of disruptive innovation in the
acute care pathway
 Acute assessment by ‘interface
physicians’ in a community
hospital
Co-located services
Minor Injuries Unit / OOH base
Plain X-ray
Post acute care wards
(stroke, hip #, generic)
relationship with acute Trust

Delivering acute assessment and treatment
out of hospital
• Shopfloor Disciplines
 Nursing
 Physiotherapy
 Occupational therapy
 Social work
 Transport
 Medical – ‘interface capability’, drawn from 1°and
2°care clinicians
• Rapid diagnostics for senior led decisions

Point of care diagnostic tests

POC testing and culture of workforce
• Staff see POC testing as integral to running of
unit
• Consensus of value and purpose of POC testing
• Operational hassles overcome as a result

How can we select patients for ambulatory
care? The state of the art…..
• Outcome = discharge
within 12 hours of
referral to medicine
• Independent predictors
summed into the Amb
score
Ala et al 2012 Clin Med 12(5) 420-6

Patient and carer experience of acute
ambulatory care

New Models of Care with POC diagnostics
• Re-engineer community health infrastructure
• Providing credible care in new locations means delivering
processes of care there too
• Identification of appropriateness for ambulatory care
needs more evidence – very little ‘evidence based
location of care’

Closing Keynote
Dr Tony Newman-Sanders
Clinical Director, Diagnostic Imaging, NHS England

www.england.nhs.uk
Tony Newman-Sanders
MA FRCR FRCP
National Clinical Director -
Diagnostics
NHS England
Diagnostics: An
NHS England
Perspective
6/11/17

www.england.nhs.uk
1. NHS England –
Strategic objectives
2. NHS England
Diagnostic policy areas
3. Overview of the day
4. NCD – wider role and
relations
5. Summary
Overview
190

www.england.nhs.uk 191
Imaging /
Radiology
For example, X-
Ray, MRI and
Ultrasound
Determining body
structures using a
variety of non-
ionising and
ionising radiation
Mainly delivered in
hospitals, including
for primary care,
and in delivering
some therapeutic
interventions,
some private
provision for NHS
Pathology
Services
For example,
biochemistry, and
histopathology
testing
Assessment of body
composition,
microbial
assessment and
therapeutic markers
through blood,
cellular and tissue
samples
Mainly delivered by
hospital labs,
including for primary
care - some
near-patient testing
Genetics &
Genomics
Analysing the
genetic code.
From single gene
testing and arrays to
full genomes, and
other functional
genomic
investigations, for
example RNA and
transcriptomics.
Primarily delivered
through regional
genetic laboratories
Physiology
For example,
audiology,
respiratory and
cardiac
Measuring the
performance of
aspects of the
body’s function and
the restoration of
function
Mainly delivered in
hospitals, some
directly in primary
care, by 8 different
clinical specialities
Endoscopy
For example,
bronchoscopy and
colonoscopy
Optical examination
of the inside of the
body, sometimes
linked to therapeutic
procedures
Primarily delivered
in hospitals
• Approximately 1 billion diagnostic tests undertaken each year, circa £8 billion on NHS spend.
• Diagnostic services are currently categorized into 5 pillars based on similarities in primary function or measurement techniques.
• Within this there are over 100 discrete areas of service provision which are often viewed and treated as separate service
entities despite common cross-cutting issues and involvement of multiple diagnostic services in care pathways.
The Five Diagnostic Pillars

The strategic importance of diagnostics:
• The Five Year Forward View sets out the aim of accelerating useful health innovation and taking steps to speed up
innovation in diagnostics.
• However, the 2nd Atlas of Variation in NHS Diagnostic Services in England highlights significant geographical
variation and inequality in access to diagnostic tests and investigations (in some tests up to a [50 fold] difference),
which can be linked to poor outcomes in some conditions including cancer in local populations
• The Atlas of Variation in NHS Diagnostic
Services in England brings together information
on geographical variation in diagnostic testing.
highlights wide geographical variation in levels of
service provision, efficiency and quality.
• Both the 1st (2013) and 2nd Atlas (Jan 2017)
highlight significant geographical variation and
inequality in access, which can be linked to poor
outcomes in some conditions. This is despite
recommendations for the investigations by NICE
and in other guidelines
.
• Many of the reasons for variation in service
provision are common to all disciplines across
diagnostic services, such as patterns of disease
prevalence, the availability of a trained workforce
and local custom and practices, whereas others
are different, arising from the differences in the
nature of the specific interventions and tests.
• Whilst the 2nd Atlas provides some key data on
variation, it was not possible to update data on
pathology and genetics services.
Five Year Forward View like.
• Delivering the Forward View –
Diagnostics is reflected in:
• NHS England Mandate 2016-17
• NHS planning guidance 2016/17 –
2020/21
• The NHS England’s business plan
for 2016/17
• NHS Operational Planning
• Contracting Guidance 2017-2019
• Diagnostics are key to the delivery of a
number of key priorities across the NHS:
• Cancer
• Mental health and dementia
• Learning disabilities
• Diabetes
• They are vital in:
• the drive towards Seven Day
Services
• Delivering the Urgent and
Emergency Care agenda.
• Accelerating innovation in new
ways of delivering care
Diagnostic landscape

The importance of diagnostics in addressing wider issues:
Several reviews of the NHS and the health care system more widely have identified national and global issues
and opportunities, that can only be tackled with concerted improvement of our diagnostic services
Achieving World Class Cancer Outcomes - The Independent Cancer
Taskforce noted that science has advanced to a point where we can
increasingly predict the risk of developing cancer, the response to
treatment and the overall prognoses for cancer patients using molecular
diagnostics. It called for an increase in molecular diagnostic provision.
Carter’s Review of Operational productivity and performance in
English NHS acute hospitals - Estimated that unwarranted variation in
non-specialist acute hospitals is worth £5bn in efficiency opportunities
and variation in diagnostic efficiency and productivity is contributing to this
(~£200m in pathology).
Review on Antimicrobial Resistance, O’Neill- New rapid diagnostics are
needed to identify whether a patient will benefit from an antimicrobial and
whether clinicians are dealing with a resistant strain.
Building our Industrial Strategy and Accelerated Access Review -
Recommendations on how to accelerate access for NHS patients to
innovative medicines, medical technologies, diagnostics.
NHS England Priorities :
• Urgent and Emergency Care Review
• Seven Day Services
• Referral to Treat / waiting times
• Early diagnosis
• Learning disabilities and mental health
• Personalised Medicine
Strategic importance

The overarching vision is to align our approach to diagnostics to support the move towards personalised medicine
Vision – personalised medicine
Imaging
Biochemical &
biomarker data
Tissue
samples
Physiological tests
Genomic sequence data
Multi-omics information
Eg metabolomics, epigenetics
Clinical, population, social,
economic data
Individualised
and integrated
diagnostic and
clinical
phenotype at
one point in
time and over
time
Leading to the best use
of medicines,
supporting better
patient outcomes and
efficiencies

Diagnostic Policy Areas
• Quality
• Accreditation
• Point of Care
• AMR. Response to O’Neill Report
• 7 Day Services –with focus on USS, MRI, echocardiography and
interventional radiology
• Cancer.
• 28 day referral to diagnosis/exclusion
• Referral to treatment; 62 day
• Identifying optimal pathway e.g. Lung CT
• Straight to Test – Colonoscopy / Colorectal CT scan
• Senior Clinical Triage
• Digital Diagnostics
• Models of Service provision and underpinning Commissioning models.

Accreditation
• ISAS is a patient-focused assessment and accreditation program
designed to help diagnostic imaging services ensure that their
patients consistently receive high quality services, delivered by
competent staff working in safe environments.
• NHS England has outlined its strong position towards accreditation
of diagnostic services by publishing a position statement. It remains
committed to, and strongly endorses participation of diagnostic
services in the ISAS scheme.
• UKAS assesses imaging services against the ISAS Standard and
ensures that required standards are maintained through regular
monitoring. An enhanced package of pre-application support is
available to all services, as well as an optional staged pathway to
accreditation during the initial assessment.
• CQC explicitly recognises the assurance of ISAS as part of their
inspections

www.england.nhs.uk
Test Actions to ensure delivery
CT Ensure weekend capacity meets weekend demand.
Microbiology None required, although be aware of new acute micro tests becoming available
in next few years to help reduce AMR.
Ultrasound Training and recruitment of more sonographers, and in some specialties such as
obstetrics and gynaecology, skill-sharing with other related acute professions.
Echocardiography HEE plans to train appropriate acute staff, including cardiology trainees as part
of their sub-specialty training, to use echo as part of their range of skills, but it
will take longer than two years for staff with these skills to be in place across all
hospitals. Separate work also needed to ensure that all hospitals with on-site
cardiology services have echo-trained cardiologists on site over weekends.
Upper GI
endoscopy
Encourage trust to build in weekend emergency capacity locally or via a network
(noting that the emergency endoscopy capacity must be on same site as the
acutely bleeding patient).
MRI Provide clarification for the survey of indications and encourage networked
provision (usually patient can travel by ambulance if necessary).
Haematology,
biochemistry
All basic acute tests already available. No action required.
The 7DS Programme has a priority clinical standard to ensure that key
diagnostic tests are available to all patients admitted to hospital in an
emergency by 2020
Standard 5 – Timely access to diagnostics: Hospital inpatients must have scheduled seven-day access to
diagnostic services . Consultant-directed diagnostic tests and completed reporting will be available seven days a
week within 1 hour for critical patients, 12 hours for urgent patients and 24 hours for non-urgent patients

www.england.nhs.uk
Cancer Diagnostics
198
• National Cancer Programme Clinical Steering Group
• Optimal diagnostic pathway design e.g. Lung, Colon,
Breast
• Prostate Clinical Expert Group
• Straight to test; Colon cancer.
• Referral to treat; 62 day target. Remains a key priority
• Earlier diagnostics
• New delivery models;
• Sustainability and transformation fund
• Primary care and increased awareness
• Networked diagnostics
• Multi disciplinary Diagnostic Centres
• Pilot of 28 day standard; Referral to diagnosis

www.england.nhs.uk
Future models of Service Delivery;
What is the future for diagnostics?
199
FUTURE
DIAGNOSTIC
PROVISION
At home
or in the
High Street
Tele-
monitoring
of
individuals
Local
Diagnostic
Hubs
Tertiary
Care
Tele-
reporting &
image/ data
sharing
Specialist
Diagnostic
Centres
24/7 & 7day

www.england.nhs.uk
Emerging areas of focus
200
• Sepsis
• Implications for interventional radiology
• Artificial intelligence
• Electronic decision support systems
• Several well known companies providing differing
perspectives;
• CAD
• Structured and unstructured data

www.england.nhs.uk
NCD and benchmarking
201
• Work with NHS Benchmarking, Rightcare and GIRFT to
get a validated picture of what good diagnostic
performance looks like
• Understand any variation
• Data
• Local factors and resource issues
• Correlate with other data eg 7 day survey
• Balance Performance with Quality
• Understand main opportunities for improvement
• Commissioning levers
• New Models of Care
• NHSI and others

Digital Diagnostics
• New Programme Board
• Chaired by Chief Scientific Officer
• Clarity about roles of NHSE, NHS Digital and
Genomics England
• Architecture to support future vision and current
needs for interoperability
• National Information Board
• Strategic Clinical Reference Group
• Information and Digital Technologies Clinical
Requirements 2020,

www.england.nhs.uk May 2017§203
The DID compiles record-level data from NHS Radiology Information Systems (RIS) relating to
diagnostic imaging activity in hospitals in England. It fulfils a requirement from the Government’s 2011
Improving Outcomes: A Strategy for Cancer to collect data on GP usage of key tests for cancer, to
benchmark and improve access for early diagnosis.
The data are collected by NHS Digital on a monthly basis. They are linked to Hospital Episodes
Statistics for fuller analysis of acute secondary care pathways. NHS users may apply for access to the
DID via NHS Digital’s iView reporting tool. Details of this and the collection are at:
http://www.hscic.gov.uk/DID
Results are analysed and published by NHS England in provisional monthly summary reports and a final
annual release, at:
http://www.england.nhs.uk/statistics/statistical-work-areas/diagnostic-imaging-dataset/
The DID captures information about the:
• Test, including type of test and body site (using NICIP and/or SNOMED CT coding schemes);
• Patient, including demographics and identifiers for linkage to other datasets;
• Referral source, eg GP direct access, outpatient, A&E and referrer details;
• Waits, eg from date of request to date of test and period from test to the report being issued;
• Organisation, the hospital provider, GP practice and commissioner.
Digital Imaging Data

www.england.nhs.uk May 2017204
What tests are covered?
All imaging activity is coded, but the grouped modalities commonly reported are:
● X-ray ● MRI ● PET scans
● Ultrasound ● Fluoroscopy ● SPECT scans
● CT scan ● Nuclear Medicine ● Medical photography
Although we don’t know which actual tests were used to diagnose or rule out Cancer, we report on the following tests that
could contribute to the early diagnosis of cancer:
● MRI of Brain ● X-ray of Chest
● Ultrasound of Kidney or bladder ● Ultrasound of Abdomen and/or pelvis
● CT of Chest and/or abdomen
What statistics are produced?
Eg Volumes and trends; ‘Wait’ times; ‘Turnaround’ times
Ultrasound activity by number of
days from date of test request to
date of test, by source of referral,
2015-16
Average period
from date of test to
date test report
issued for Chest X-
ray, by provider,
2015-16
X-ray Ultrasound CT Scan MRI
Fluoro-
scopy
Female 11,982,320 6,352,960 2,189,130 1,631,900 506,045
Male 10,187,900 2,394,195 2,207,880 1,415,245 523,480
Not known /
specified
404,375 181,775 64,565 39,070 11,030
0-14 1,998,165 409,560 52,610 131,490 54,020
15-44 5,261,755 4,385,080 734,230 962,430 186,900
45-59 4,542,165 1,697,510 893,380 856,845 238,430
60-74 5,368,395 1,374,265 1,328,970 750,830 316,505
75+ 5,087,755 954,020 1,393,935 358,135 233,175
Not Known 316,365 108,495 58,455 26,475 11,535
NHS Imaging by gender and age, 2015-16
Digital Imaging Dataset

www.england.nhs.uk May 2017205
Diagnostic performance
0.7%
1.0%
0.3%
0.3%
0.1%
1.2%
2.5%
1.9%
0.8%
2.3%
8.6%
3.1%
2.8%
4.5%
2.2%
0% 3% 5% 8% 10%
MRI
CT
US
Barium Enema
Dexa Scan
Audiology…
Echocardiogra…
Electrophysiol…
Peripheral…
Sleep Studies
Urodynamics
Colonoscopy
Flexi-…
Cystoscopy
Gastroscopy
0.5%
2.0%
2.9%
Total Imaging
Total…
Total Endoscopy
Current Performance
Figure 1: Current performance of diagnostic tests
against the 1% standard – breakdown of tests
0%
1%
2%
3%
Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar
Diagnostic Performance
Standard 2015/16 2016/17
Overall, diagnostic performance decreased to 1.1% in
March 17, from 1.% in February 17 but is better than
March 16 (1.7%). However the national standard of
1.0% was not met.
Overall the 1% standard has not been met since
December 2013.
Figure 2: Overall current performance of
diagnostic tests against the 1% standard

Waiting lists
750,000
800,000
850,000
900,000
950,000
Apr
May
Jun
Jul
Aug
Sept
Oct
Nov
Dec
Jan
Feb
Mar
Total Waiting List
2015/16 2016/17
• The total waiting list is 934,010, up 47,000 from February 17.
Compared to the same month last year it has increased. This trend
has been consistent historically
• Demand is therefore outstripping capacity with waiting lists
increasing

www.england.nhs.uk
NCD wider role
207
• Expert advice to NHSE;
• Royal Colleges
• Radiologists
• Anaesthetists, Surgeon, Emergency Medicine etc
• SoR
• Health Education England
• NHS Digital and National Imaging Board
• SCRG
• NHS Improvement
• GIRFT
• Imaging Transformation
• Connecting to regional teams

www.england.nhs.uk
Overview of the day
208
• Business case.
• Commissioning levers.
• Current diagnostics delivery by private sector
• MRI scanners
• OOH reporting
• App development and data
• Delivering diagnostics in new ways.
• POC imaging in ITU and ED Challenge of 24/7 echo.
• FIT for symptomatic patients
• POC for STDs viral illnesses; COPD exacerbations
• Multi disciplinary diagnostic and assessment centres
• Ambulatory care diagnostics.
• Genomics to deliver genuinely personalised diagnosis of cancer
• Innovation and Technology tariff

www.england.nhs.uk
Key messages
209
• Importance of Diagnostics has never been more widely
recognised
• Vision of truly personalised medicine will have a major
impact on the way we think about diagnostic imaging
• Maximum value from treatments especially medicines
• There are significant and growing challenges to meeting
the expectations of colleagues and patients
• Key policy drivers will help meet some of these
• Need to work creatively together to articulate and meet
some of the others
• NCD doesn’t have all the solutions but is uniquely placed
to work across the system to try and find solutions

UK Diagnostics Summit Presentations

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UK Diagnostics Summit Presentations