Dr Andrew RoseMCRN Deputy Assistant Director

Driving Research Collaboration through NIHR Clinical Research Network: Focus on NIHR Medicines for Children Research Network

NIHR Research Infrastructure

> £0.5 billion p.a. investment in relevant infrastructure to support clinical research at all points in the development pipeline

Ravi Chana/Oliver Rausch (NOCRI)

Late-phase clinical research

NIHR Biomedical Research Centres

Early-phase clinical research

Invention Evaluation Adoption

NIHR Biomedical Research Units

NIHR Clinical Research Facilities

Experimental Cancer Medicine Centres

NIHR Clinical Research Network

NIHR Health Technology Cooperatives

NIHR Diagnostic Evidence Cooperatives

NIHR CLAHRCs

EU Regulation “Better medicines for children”

• Became law in across EU on 26 January 2007• Incentives and requirements for industry to undertake

paediatric studies• Paediatric Committee

– Based in European Medicines Agency• Paediatric Investigation Plan (PIP)

– Development agreed with Paediatric Committee• Coordinated European Paediatric Trials Network

3

To improve children’s health and alleviate suffering through the provision of better and safer medicines

MCRN’s Vision

AIMS• The best infrastructure in the world to support studies which

address the safety and efficacy of medicines for children.• An excellent base for clinical research for children which is an

attractive resource for the global pharmaceutical industry.• To ensure that world-leading research addresses the needs of

children.

NIHR Medicines for Children Research

Network• Large network supporting randomized and other studies of

medicines for children in NHS sites• Work closely with Clinical Research Facilities (CRFs) etc• Supporting:

– All phases– All therapy areas (except oncology)

• Studies supported by MCRN– Industry-sponsored/funded– Publicly-sponsored, including

• Investigator-initiated (industry supported) Research (IIR)– Publicly-funded industry and academic/NHS consortia

5

Clinical Studies Groups (CSGs)

1. Allergy, Infection and Immunity (BPAIIG) Prof Saul Faust2. Anaesthesia, Intensive Care and Cardiology Dr Mark Peters3. Cleft and Craniofacial Anomalies Ms Rona Slater(Craniofacial Society of GB & I/The Healing Foundation)4. Diabetes and Endocrinology (BSPED) Prof Timothy Barrett5. Gastroenterology, Hepatology & Nutrition (BSPGHAN) Prof Stephen Allen6. General Paediatrics (including Dermatology) (BAGP) Dr Alastair Sutcliffe7. Inherited Metabolic Disorders Dr Chris Hendriksz(UK LSD Patient Collaborative Group)8. Methodology Prof Ruth Gilbert9. Neonatal (Action Medical Research) Dr Mark Turner10. Nephrology (BAPN) Dr Richard Coward11. Neurosciences Prof Helen Cross12. Pain and Palliative Care (Louis Dundas Dev’ Fund) Dr Richard Howard13. Pharmacy and PharmacologyProf James McElnay14. Respiratory and Cystic Fibrosis Dr Paul Seddon15. Rheumatology (Arthritis Research UK) Prof Michael Beresford

6

LRN/Area staff support the conduct of paediatric research in the NHS and work in accordance with Good Clinical Practice (GCP)

• Director• Manager• Research Nurses• Pharmacists• Data entry staff• Administration

Local Research Networks (LRNs) and Areas

7

Growth of Portfolio

8

Recruitment to studies

9

Num

ber o

f par

ticip

ants

recr

uite

d

Recruitment totarget (2012/13)

10

Support for industry-sponsored and funded

studies• Dedicated MCRN Industry Staff• Facilitate close working with companies and contract research

organisations (CROs)– Interacted with close to 200 companies interested in children’s

research• Detailed knowledge of/access to expertise

– EU Paediatric Regulation (PIPs)– Study and programme design (inc pharmacy)– Implementation (feasibility, set-up, delivery)– Consumer matters (patient information etc)

industry@mcrn.org.uk

11

NIHR CRN Feasibility Services

1. Early Feedback– A rapid assessment of feasibility (10 days) by clinical specialists:

• Current UK practice, prevalence of the relevant patient population• Network knowledge of competing studies etc.

2. Site Intelligence– Sites selected - process ensures that proposed recruitment targets are

realistic (15 days)• Complements existing feasibility data• In parallel with other processes (study added to portfolio)

3. Site Identification– Identification of new sites (15 days)

supportmystudy@nihr.ac.uk

12

Growth of Industry Portfolio

13

update

Industry-sponsored and funded case study 1

• Systemic Juvenile Idiopathic Arthritis– Sponsored by F. Hoffmann-La Roche Ltd (Roche)

• Tocilizumab in children aged 2 to 17• Interactions between Rheumatology CSG and company• Despite significant challenges, the MCRN recruited on time

and to target• Product now

– Licensed for use in this setting and– Approved by National Institute for Health and Clinical Excellence

(NICE)• Programme of related research with tocilizumab

14

Industry-sponsored and funded case study 2

• Study to evaluate an antibody for the treatment of neonatal sepsis (Biosynexus)

• 93 international sites (8 UK)• MCRN staff/resources supported:

– Site identification (CRO found challenging)– Ethics approval– Site setup (costing/approvals/logistics)– Recruitment

• Success in this and other neonatal studies have helped to attract other studies

15

Licensed Products

• Prevenar 13 vaccine/Pneumococcal disease• Cozaar/Proteinuria• Tocilizumab/systemic juvenile idiopathic arthritis (sJIA)• Xalatan (Latanoprost)/Glaucoma• Menveo vaccine/Meningococcal disease• Kalydeco (Ivacaftor)/Cystic fibrosis (G551D)• More in the pipeline...• Others no paediatric indication, but info added to SPC

16

Investigator-initiated (industry supported)

Research (IIR)• Publicly (NHS/Uni)-sponsored and led, with industry support:

– Academic investigator develops protocol and approaches industry for:– Funding, drug, placebo, device and/or other support– Uni/NHS act as sponsor

• Industry benefits– To support “research that advances medical and scientific knowledge

about our products and that generates promising medical interventions” Pfizer.com

– Retain product IP• Academic benefits

– Access to products, funding etc to conduct research for the benefit of patients

17

Investigator Studies Operations Group

(ISOG)

• UK Pharma Industry Group (with NIHR representation)• Discusses challenges with investigator-initiated studies• Working to standardise IIR contracts• Meets several times per year

• Investigator Initiated-Sponsored Research Association (IISRA)

18

IIR case study

• SYCAMORE• RCT of Adalimumab in combination with Methotrexate for

the treatment of juvenile idiopathic arthritis associated uveitis– Clinical effectiveness, safety and cost effectiveness

• CI - Dr Athimalaipet Ramanan• Sponsor - University Hospitals Bristol NHS Foundation Trust• Funders

– NIHR Health Technology Assessment– Arthritis Research UK

• Active and placebo provided by Abbvie (Abbott)

19

Industry and academic/NHS

consortia studies

• Publicly funded:– EU FP7, MRC, NIHR Invention for Innovation (i4i) etc– Industry or public (NHS/University) sponsorship

• Collaborative development of protocols/programmes• Industry benefits

– Obtain funding, develop academic links, develop company expertise, IP and products, commercialisation opportunities

• Academic/NHS benefits– Obtain funding, develop industry links, develop Uni/NHS team

expertise, helps get products to patients, financial benefits (royalties/IP)

20

Industry and academic consortia case study

• Stratified medicine– Duchenne muscular dystrophy (DMD)– Collaboration including experts from London,

Newcastle and Serepta Therapeutics (formerly AVI)• Study team (with support of NIHR infrastructure)

designed and validated antisense oligonucleotides (“molecular patches”) for DMD gene

• MCRN/CRF and other NIHR resources supported clinical study

• Sponsor - AVI BioPharma• Funders - MRC and AVI BioPharma• Encouraging early results

21

Children’s Research Industry Group (CRIG)

• Direct MCRN links with industry previously not formalised• Established CRIG, for MCRN/wider NIHR to:

– Improve collaboration with industry– Improve the support that we offer industry– Obtain support and advice on industry matters– Provide a forum for the discussion of children’s research issues of relevance to

industry• Membership

– Pharma– CRO– Med tech

• Meetings 10 May 2013 and 23 September 2013• Next early 2014

22

industry@mcrn.org.ukwww.mcrn.org.uk

23