NIHR funding opportunitiesEME and HTA programmes

Dr Sarah PuddicombeAssistant Director

NIHR Evaluation Trials and Studies Coordinating Centre (NETSCC)

• Overview of NIHR• EME and HTA Programmes• Funding process • What makes a good application• How to engage with NIHR

– Submitting research suggestions– Reviewing priorities and funding applications

Overview

The NIHR Health Research System

The central role of NIHR research in the innovation pathway

INVENTION EVALUATION ADOPTION DIFFUSION

Biomedical Research Centres

Basic Research

National Institutefor Health Research

This pathway covers the full range of interventions - pharmaceuticals, biologicals, biotechnologies, procedures, therapies and practices - for the full range of health and health care delivery -prevention, detection, diagnosis, prognosis, treatment, care.

Patient Safety Translational Research Centres

Research for Patient Benefit

Programme Grants for Applied Research

Health Technology Assessment

Invention for Innovation

Collaborations for Leadership in Applied Health Research and Care

Dissemination Centre, Cochrane, TARs

Development Pathway Funding

Public Health Research

Health Services and Delivery Research

Efficacy & Mechanism Evaluation

NHS Commissioning Board and Clinical Commissioning Groups Commissioning

National Institute for Health & Care Excellence Guidance on Health & HealthcareNHS Supply Chain Support for Procurement

NHS Evidence Access to EvidenceInnovationAcademic Health Science Networks

Patient CareProviders of NHS Services

Clinical Research FacilitiesExperimental Cancer Medicine Centres

Horizon Scanning Centre

Centre for Surgical Reconstruction & Microbiology

Biomedical Research Units

MedicalResearch Council

Healthcare Technology Co-operatives

Research Schools

• Research with the capacity to improve patient and public outcomes and NHS services

• Multiple methodologies (not only RCTs)

• Not– Discovery science– Work involving animals or animal tissue

What is applied research?

Which funding programme?

http://www.nihr.ac.uk/documents/about-NIHR/NIHR-Publications/Funding-Opportunities-Booklet.pdf

Managed translational pathway

Overview of NETS programmes- since 2012

NETS

Public Health Research (est 2008)Public health interventions outside the conventional health service.Trials in community settingsNatural experimentsEvidence synthesis and primary research

Health Technology Assessment (est 1993)Pragmatic,Clinical and cost effectivenessMainly quantitativeMainly evidence synthesis and RCTs or appropriate study design

Health Services and Delivery Research(est 2012) Models of delivery, systems research, patient experienceMainly qualitative or mixed methods

Efficacy & Mechanism Evaluation (est 2008)Funded jointly by the Medical Research Council and NIHRTranslational research brokerMainly devices and pharmaceuticalsEfficacy (e.g phase 2b) and mechanistic studies

Systematic Review(est 2012)Production and updated SRs supported by core funding UK Cochrane Centre, Cochrane Review GroupsCRD/NIHR DC and twofunding streams (CPG and CIA)

www.nets.nihr.ac.uk

Commissioned and researcher-led callsFull and appropriate funding, no upper limit (except SR)

Our approachNeeds-led

• We assess questions important to the NHS and other information consumers, and in what priority they should be answered.

Science-added• We ask does the proposal meet the scientific quality

we insist on, and how can we support the delivery of quality.

Value for money• Assessment of need and scientific support maximises

the relevance and benefits to patients, NHS and decision makers

Efficacy and Mechanism Evaluation Programme

Aim:• Support excellent clinical science with an ultimate view to improving

health or patient care

Dual Approach:• “Science driven” – examine the efficacy of a technology intervention

(i.e. pharmaceutical, diagnostic test, surgical or psychological therapies, or public health measures) and/or explore its mechanisms of action

• Clear patient focussed outcomes in areas of need for health care research

Efficacy and Mechanism Evaluation Programme

• Provide definitive evidence of efficacy of healthcare interventions, including the size of the effect and safety

• Add significantly to understanding of disease mechanisms• Break new ground – new scientific or clinical principles• Include development or testing of new methodologies• Include validated surrogate markers as indicators of outcome• Include laboratory studies as part of the main study, if relevant to the

EME remit

EME will support clinical trials and evaluative studies in patients that:

Efficacy and Mechanism Evaluation Programme

• Confirmatory studies • Studies to identify previously unknown biomarkers • Incremental modifications or refinements of existing technologies• Proof of concept studies

• Confidence in Effect

• Global Health studies

• Any research involving animals

EME does not undertake:

Study of Tolerance to Oral PeanutDr Pamela Ewan & Dr Andrew Clark, University of CambridgeOral immunotherapy can induce tolerance to peanuts in peanut allergic patients

Remote ischaemic preconditioning in renal transplantationProfessor Raymond MacAllister, University College LondonCan RIPC improve renal function after transplantation

A randomised double-blind placebo controlled Phase 2B clinical trial of repeated application of gene therapy in patients with Cystic FibrosisProfessor Eric Alton, Imperial College LondonEffectiveness and safety of monthly aerosol administration of CFTR into lungs of CF patients

EME Funded Studies

Purpose and Remit• To deliver high quality research information on the effectiveness,

costs and broader impact of healthcare treatments and tests for those who plan, provide or receive care in the NHS.

What is HTA?• The term includes all interventions used to promote health, prevent

or treat disease, improve rehab or long-term care including drugs, devices, procedures, settings of care and screening.

Evaluation Trials and StudiesCoordinating CentreHTA Programme remit

Typical HTA randomised controlled trial:

o Multidisciplinary and multi-centreo Effectiveness and cost-effectiveness (usually estimate £/QALY)o Pragmatic and externally valido Median number of patients = 700 (Range of 15 to 75,000 across

current projects)o Average duration ~4 years and £~1.2 mo Protocols available on web site with costs

Types of studies funded:o randomised controlled trials and non-randomised trialso stand-alone pilot and feasibility studies (where there is evidence

they will lead to a full trial)o cohort studies (retrospective or prospective)o adaptive and efficient study designs, methodological studieso evidence synthesis and modelling studies

Treatment of severe ankle sprain: a pragmatic randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of three types of mechanical ankle support with tubular bandage. The CAST trialProfessor Matthew Cooke and Professor Sallie Lamb, University of Warwick

CRASH2 Trial, a large randomised placebo controlled trial among trauma patients with significant haemorrhage of the effects of an antifibrinolytic treatment on death and transfusion requirementProfessor Ian Roberts, London School of Hygiene and Tropical Medicine

PD MED, A large randomised assessment of relative cost effectiveness of different classes of drugs for ParkinsonsDr Richard Gray, University Oxford

HTA Project Examples

Topic identification - for commissioned calls

• External Engagement (Royal colleges, clinical networks, speciality groups, charities)

• Stakeholder engagement (e.g. DH, NICE, patient organisations, National Horizon Scanning Centre)

• Panel members/ Chairs (suggestions and ID activities at panels)

• James Lind Alliance PSPs• Literature searches ( publications/NIHR final reports)• Data base scanning (Cochrane, DARE, DUETS)• Webform for public and professional suggestions:http://www.nets.nihr.ac.uk/identifying-research/make-a-suggestion

Potential EME topics

Commissioned- Potential Calls

Check out the pipeline of potential topics for future commissioning(in ~6-12 mths) on our programme funding pages

Potential HTA topics

Funding Streams• Commissioned workstreams

– Identification of clinical uncertainties by the research programme– Start with an assessment of importance to the NHS– Topics are refined and prioritised by people with expertise in the field, and

commissioning briefs are advertised– Applications are assessed for compliance with the commissioning brief,

scientific quality, feasibility and value for money

• Researcher-led workstreams– Open calls for researchers to apply for funding for their own questions – Applications are prioritised in terms of NHS need in a process similar to that

in the commissioned workstreams– Applications are then assessed for scientific quality, feasibility and value for

money

Efficacy and Mechanism Evaluation Programme

Types of Research

Primary Research;Clinical efficacy of interventions

Primary Research;Clinical efficacy of interventions

Who defines the question?

EME Programme

Researcher

Frequency Per year

3 submission deadlines

Continuous with 3 submission deadlines

Researcher- led

Commissioned

Efficacy and Mechanism Evaluation Programme

• Research areas identified using a broad range of sources • Previous calls include:

Diagnostics to support stratified medicineNovel imagingCOPDPancreatitisRetinal diseasePre-eclampsia

• Calls pre-advertised for 6-12 months before a commissioning brief is published for each new call

• Webinars held for each commissioned call• Application Process – 3/yr (several calls open at once) • Check the website: www.nets.nihr.ac.uk/funding/eme-commissioned

Commissioned work stream

Efficacy and Mechanism Evaluation Programme

• Need to be fully worked up and embedded in the main study

• Should be hypothesis driven with a feasible research question

• Should aim to advance scientific understanding of the disease mechanism or the mechanism of action of the treatment

• Discovery of new biomarkers is not within the remit of the EME Programme.

Mechanistic studies – optional but encouraged in all efficacy studies

Efficacy and Mechanism Evaluation Programme

In addition:• Studies must utilise patients or samples from current or completed

NIHR-funded or NIHR-managed studies in any setting.• The research relevant to the intervention and outcomes proposed

by the original study and add significantly to the scientific understanding of the mechanisms of action of the Intervention

• May involve the analysis or reanalysis of previously stored specimens or data, or the collection of new specimens or new data for additional analysis, provided it is obtained from study participants.

Stand alone mechanistic calls for funded NIHR studies

EME funding process

Types of Research

Specific technologyassessment

Primary researchFeasibility & pilotEvidence synthesis

NICE

Researcher

Primary researchEvidence synthesis

Theme from HTAProgrammeQuestion from researcher

Continuous with3 closing dates

Primary researchFeasibility & pilotEvidence synthesis

HTA Programme 3 calls

1-2 calls

Direct referral toOn-contract teams

Who defines the question?

Frequency Per year

Commissioned

Evaluation Trials and StudiesCoordinating Centre

NICE Guidance

Researcher-led

Clinical Evaluation

Themed Calls

Health Technology Assessment

Overview of HTA application processTwo stage process (outline & Full)Pilot in HTA -Short EoI form instead ofoutline application

Panels consider importance/needBoard consider scientific quality, feasibility, host, team and value for money

External peer and public reviewTimeframe submission to final decision:~ 3.5 months Evidence Synthesis (straight to full- one stage)~7.5 months Primary ( outline and full- two stage)

http://www.nets.nihr.ac.uk/funding

Close Programme Call1st July 15 EME 15/48 Researcher-led3rd Sept 2015 HTA 15/57 Researcher-led Expressions of Interest3rd Sept 2015 HTA 15/58 Researcher-led Evidence Synthesis Full24th Sept 2015 HTA 15/39 - Treatment of avascular necrosis of the femoral

head24th Sept 2015 HTA 15/40 - A clinical decision aid to inform the management of

lower urinary tract symptoms in men in primary care24th Sept 2015 HTA 15/41 - Interventions for adults with spasticity due to

Cerebral Palsy24th Sept 2015 HTA 15/42 - Multi-modal retinal imaging for surveillance of

patients with treated diabetic eye disease24th Sept 2015 HTA 15/43 - Extended rehabilitation for older frail people after

acute illness or injury10th Nov 2015 EME 15/73 Markers of early treatment response in non-

cancerous conditions10th Nov 2015 EME 15/74 Novel diagnostics and treatments for irritable bowel

syndrome10th Nov 2015 EME 15/75 Mechanisms of action of health interventions

Evaluation Trials and StudiesCoordinating Centre

• Important to the NHS or addressing an information need• Research focused on patient outcomes and quality of life• Timely and supported by current evidence • Structured to provide clear, well-defined question (PICO)• Provides value for money with realistic costing• Plausible recruitment and retention• Demonstrated PPI engagement at all stages• RDS/CTU engagement (as appropriate)• Good quality plain language summary• Well proof read • http://www.youtube.com/NIHRtv

What makes a good research application?

Tips for success

Commissioned • Check our regular adverts

on hta.ac.uk and eme.ac.uk

• Subscribe to call notifications

• Minimum of 8 weeks to respond to an advert

– You must be quick – the board recognises this

Researcher-Led• Put together a compelling

and robust application to answer an important researcher question

• Submit it when it’s right– It’s better to submit the right

application, than a quick application.

Tips for success

• Read the detailed brief for the call, the Guidance notes and the FAQs www.nets.nihr.ac.uk/funding

• Check application fits within the programme remit www.nets.nihr.ac.uk/faqs/remit

• Check against the existing portfolio of research

http://www.nihr.ac.uk/research/programme-studies.htm

and UKCRN portfolio: http://public.ukcrn.org.uk/search/

• Use online resources Webinars/ help videos: www.nets.nihr.ac.uk/resources/

• Please contact programme secretariat for advice

Efficacy and Mechanism Evaluation ProgrammeIssues commonly discussed by the Board (1)

• Research question – the question needs to be in remit and clearly defined in simple terms, ideally in one sentence

• Importance – of this project needs to be explained

• Justification – needs references or preliminary data

• Patient and public involvement is expected from the design stage through to delivery and dissemination of research

• Multi-disciplinary team – including clinical staff, researchers, statisticians and experts in study design

• Research Design Service/Clinical Trials Unit – consult early

Efficacy and Mechanism Evaluation Programme

• Study design – needs to be optimised to answer the question

• Outcome measures – justify your choice of primary outcome and any secondary outcomes

• Sample size/power calculation – provide enough data to allow the calculation to be repeated

• Recruitment plan – make sure this is credible by including eligible number of patients, drop-out rates and recruitment targets

• Drug dose/side effects – need to be clearly explained for drug studies

• Costs – these need to clearly justified, especially high-cost staff such as clinicians

Issues commonly discussed by the Board (2)

How can I get involved?• Suggest future research topics anytimehttp://www.nets.nihr.ac.uk/identifying-research/make-a-suggestion

• Professional and public contributors welcomed:• Become a reviewerhttp://www.nets.nihr.ac.uk/become-a-reviewer/reviewer-form• Apply for advisory roles openly advertised on website e.g.

Panel member/Board member

• Join our mailing lists for programme and funding bulletins• http://www.nets.nihr.ac.uk/news/bulletins

• For general information on NETSCC and our work– info@netscc.ac.uk or www.netscc.ac.uk

• Always willing to answer questions on remit

• EME Programme– info@eme.ac.uk or www.eme.ac.uk

• HTA Programme– hta@hta.ac.uk or www.hta.ac.uk

Contact details

Evaluation Trials and StudiesCoordinating Centre

Puddicombe Way : A dedication to Mima Puddicombe, OBE. Former Matron of Addenbrookes 1958-1970, who died in 2005. Pictured meeting the Queen in 1962.

Thank you for listeningAny Questions?

Supplementary slides

• Launched 2008• Recognises the crucial role played by CTUs in designing and delivering

quality NIHR research applications and projects• Provides ‘priming’ funding to support CTUs on a 3 year rolling contract and

provides stability to units, allowing expansion and retention of skilled staff• Intended to result in an increased number of high quality research

applications submitted to NIHR programmes• 22 CTUs in England supported to date on rolling contract basis• Funding adjusted according to successful grant applications

Clinical Trials Unit Support Funding

Evaluation Trials and StudiesCoordinating Centre

Success rates

16% EME 2014/15( 1/3 out of remit and 2/3 rejected at outline)18.7 % HTA 2014/15

Expert Review

HTA Research Recommendations ?

Topics

HTA Panel prioritises topic

Methods Group checks design

HTA Prioritisation

Group

Commissioning Board

6 Advisory Panels

Dissemination HTA monograph Peer reviewed

publications Conferences

Research

Proposals received

Vignette developed

Commissioning Brief advertised

Prioritisation Group

DH Funding Approval

– Pieces of research done before a main study– Used to estimate important parameters that are needed to

design the main study– Feasibility studies for randomised controlled trials may not

themselves be randomised– They do not evaluate the outcome of interest; that is left to the

main study

Feasibility studies are:

Evaluation Trials and StudiesCoordinating Centre

• A small scale version of the main study that runs to test whether the components of the main study can all work together

• Focused on the process of the main study, for example recruitment, randomisation, treatment, and follow-up assessments

• An internal pilot is a pilot that may be the first phase of the substantive study and date from the pilot phase may contribute to the final analysis

• An external pilot is one where the date may be analysed but set aside in respect of the substantive study

Pilot studies are:

Evaluation Trials and StudiesCoordinating Centre