Delivery of clinical trials through managed

networks

Jonathan Sheffield

CEO, NIHR Clinical Research Network

What we’ll cover

• The brief history of Research Networks in the UK

• The forces shaping studies and the priorities for Research

• Approaches to successful delivery for Research

2006: policy watershed

• National Institute for Health Research created to implement policy

– Thriving research culture– Fairness of access to research

across England– More patients and health

professionals participating– Increased industry investment– NHS as an international leader– Healthcare professionals proud to

work in a research-led, evidence-based NHS

– Health and healthcare improved by research evidence

Policy landscape has evolved

National Institute for Health Research:integrated health-research system

> £0.5 billion p.a. investment in relevant infrastructure to

support clinical research at all points in development pipeline

Network development

• NIHR Clinical Research Network in place across all therapy areas: supports an infrastructure for research

• Funding follows activity: opens up NHS to research

2001 2003 2006/7 20092005

Launch of National Cancer Research Network

Creation of Mental Health Research Network

Stroke, DeNDRoN, Diabetes and Medicines for Children Research Networks established

Primary Care and Comprehensive Research Networks created

NIHR Clinical Research Network in place

Research past…

• Research mainly centred on acute teaching hospitals

• Culyer funding• Equality of opportunity for

patients to participate in clinical studies?

• Research funders: lack of nationwide infrastructure to conduct research

Supporting the life-sciences industry in UK clinical research delivery

So what h

as

changed?

Network Infrastructure

• People– Appropriate training– Flexibility– Expertise

• Information– Infrastructure with reliable systems

• Management– Metrics and Support

One national network

• Research active engaged clinicians across all 30 therapy areas

• Detailed understanding of care pathways

Study delivery and management:Managing performance with quality

• A research-ready workforce – 10,000+ GCP-trained nurses embedded in the

National Health Service to support investigators with patient identification, screening, clinical delivery

• Proactive study management support– Study milestone schedule; monthly reviews of

recruitment, RAG rating of studies to a site level• Trouble-shooting from the inside

– Our strong relationships with clinicians and detailed knowledge of other potential sites gives you options if a study hits a recruitment problem

Study set-up

• CSP: system for gaining hospital permission– Do paperwork once only for multi-centre trials – Network staff in the National Health Service work on

your behalf, using relationships to push study set-up through on the inside

• Commercial costing templates– Transparent prices to assist planning– Speeds up cost negotiations

• Model agreements– Standard contract accepted across the NHS– Eliminates the need for lengthy legal review

Is it working?

Sources: 2011/12 NIHR CRN annual report; Guardian Clinical Research Zone

• Research is becoming more embedded

• 99% of NHS Trusts now research-active

• Progress with “hard-to-reach areas”

Key:Red 0 to 50 studiesPurple 51 to 100 StudiesBlue 101 to 200 studiesYellow 201 to 250 studiesGreen 251 to 400 Studies

NHS Trusts by number of studies recruiting patients in 2011/12

Research present…

Source: 2012/13 NIHR CRN annual report

• Patient involvement in clinical studies has increased

• 630,000 patients recruited into CRN Portfolio studies in 2012/13

Key:Yellow 0 to 500Blue 501 to 1,000Green 1001 to 5000Purple 5001 to 10,000Red more than 10,000

NHS Trusts by number of patients recruited to studies in 2012/13

EU total clinical trials

Data source: MHRA

UK

UK v the world

2005 2006 2007 2008 2009 2010 20110%

1%

2%

3%

4%

5%

6%

UK

Germany

Russia

France

Spain

Year

Nu

mb

er

of

pa

tie

nts

en

rolle

d a

s a

pe

rce

nta

ge

of

the

Glo

ba

l T

ota

l

• Patient enrolment per year, by country as a percentage of the Global Total.

Data source: Anonymous CRO - there is no single source for patient recruitment data, however, this graph shows where one leading CRO is choosing to put their studies

UK Today

• Number of UK commercial trial applications received• Data source: Medicines and Healthcare products Regulatory

Agency

0

100

200

300

400

500

600

700

800

CT

A n

um

bers

Commercial Phase 2/3/4 668 665 657 646 600 588 561 635 641 553 500 497 551 618

Commercial Phase 1 201 316 263 264 232 219 211 216 177 168

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

The evidence: study set-up

• Trend: projected further 30% improvement in study set up times for 2013/14

2010/11 2011/12 Q1 Q2 Q3 Q4 Annual2012/13

0

20

40

60

80

100

120

140 Start point: validated R and D form. End point: NHS permission received at all study sitesMedian Calendar Days Taken to Obtain NHS Permission (all sites in study)

Year and Quarter

Med

ian

Tim

e to

Ob

tain

NH

S P

erm

issi

on

-

Stu

dy

The evidence: time and target

• Year on year improvement

• % of studies delivered to 100% target within 100% time has more than doubled in two years (all therapy areas)

• % even higher in some therapy areas

2010/11 2011/12 2012/130%

10%

20%

30%

40%

50%

60%

70%

Percentage of Network commercial studies recruiting to 100% target in 100% time

Stu

die

s re

cru

itin

g t

o 1

00%

tim

e &

tar

get

Year

* 63% of studies met 90% or more of their recruitment target

• 102 overlapping local networks will become 15, each covering research delivery across all therapy areas

• Boundary alignment with AHSN areas

• Will form strong working bonds with AHSNs

• Increased efficiency within stable funding

Note: map still in development and subject to change

Network has evolved at local level during 2013/114

Geographical variations

London

South Central

North West

South West

North East

West Midlands

Yorks & Humber

East Midlands

East of England

South East Coast

- 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000

14,539

13,806

13,370

13,213

11,507

11,014

10,730

9,625

9,217

4,136

Patient recruitment per million population (by SHA area)

Current Challenges

• Stratified medicines: – Intensive genotyping and

phenotyping– Larger number of smaller studies:

multi-centre and specialist in nature– Fewer patients required – but harder

to find; use of technology for feasibility becomes key

– Current “individual” investigator model may be unsustainable where only a few patients will be recruited at each centre.

Cancer Research UK Strategy 2014

“Our ambition in cancer drug development is to redefine how cancer is treated and to accelerate the delivery of the next generation of medicines to patients who need them. Our understanding of the genetic aberrations underlying cancer development and how resistance to therapies develops, underpins the large number of molecules now in development. Academic research plays a critical role in this, with new models of interaction between academia and industry driving ever faster progress.” 

Dr Susan Galbraith AstraZeneca

BIG data

• Big Data – stitches data sources together: volume, velocity, variety

• Clinical Practice Research Datalink: NIHR supported; will give the UK a unique selling point for researchers

• Clinical Research Network: linking Portfolio with NHS datasets to assist study feasibility

• CRN open data platform: dashboard tools to make our data more useful – available from summer

• “Big data’s potential in pharmaceutical R&D is enormous. Armed with vast amounts of biological data and the tools to process it – cutting-edge analytics, streaming massively parallel processing and domain-specific access and query technologies – the industry will be able to develop more effective personalized medicines. It will also be able to shift focus from reaction to prevention.” PwC: Pharma 2020 report

“Real world” studies

What future for the individual investigator?

• Increasing complexity of trials

• Need for speed and delivery

• Tracking patients

• Clinical Research Networks provide a better option whether self or organizationally mediated

Campaigning to support patient involvement

The Network campaigns to raise the level of patient and public awareness about clinical research and the role it plays in developing better treatments, and encourage patients and clinicians to engage in clinical trials

Recent campaigns include:• Mystery Shopper• OK to ask• Focus on…

Patients want to engage

• Association of Medical Research Charities consumer poll June 2011: 97% of the public believe that it’s important the NHS should support research into new treatments

• NIHR Clinical Research Network consumer poll May 2012: 82% of people said it is important for the NHS to offer opportunities to take part in a clinical research study

• National Cancer Patient Experience Survey: 95% of those who discussed research were glad to have been asked; 53% of those who did not discuss research said they would have like to have been asked

Role of www in patient recruitment

• Highly-sophisticated online patient recruitment, self-monitoring and support systems now in place

• Role of social media in driving patients to study sites

• UK Clinical Trials Gateway developing in that direction

• Customer route to research may be different in the future: patients take initiative

Conclusion

• The NIHR funding and networks are to support research throughout the NHS

• We work to support research delivery for all specialties• We are active in all NHS environments• Patients support and want to be involved in research • Further information on the networks please go to:

– www.crn.nihr.ac.uk

Final message: it’s about patients

The new treatment has given me hope. If it is successful, it will be better than winning the lottery.

Clinical trial patient