14/10/2013

Health Services Research and Clinical Trials in the NHS

RDS Liverpool 4th October 2013

Professor Tom Walley Director, NIHR Evaluation, Trials and Studies

and Director NIHR HTA & MRC/NIHR EME programme

or How to be Successful in Applying for NIHR funding

NHS R&D Strategy • To create a health research system in which the NHS supports outstanding individuals, working in world-class facilities, conducting leading-edge research, focused on the needs of patients and the public

National Institute for Health Research

Infrastructure

Clinical Research Facilities & Centres

Clinical Research Networks

Research

Research Projects & Programmes

Research Governance

Systems

Research Information

Systems

Systems

Patients &

Public

Universities

Investigators & Senior

Investigators Associates

Faculty

Trainees

Research Units & Schools

NHS Trusts

What is applied research?

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

• Clinical research (not only trials)

• Not – Discovery science – Animal

Transparent Competitive High quality Value for money Focused on outcomes

National Institute for Health Research

Principles

www.nihr.ac.uk

Contracts, NOT grants

Health and Wealth agenda

Programme

Number of Trials/total no

of projects Total Research

Costs Sample Size EME 42/68 £47,124,251 16,754 HSDR 6/64 £2,843,501 6,257 HTA 243/313 £370,311,552 518,704 PHR 16/36 £13,284,764 15,084 RfPB 185/419 £41,977,506 30,125 PGfAR 173/109/128 £205,377,882 306,091 TCC 17/641 £7,350,216 N/A

TOTALS 682 £688,269,672

893,015

NIHR Randomised Trials Indicative Overview - October 2012

74 say feasibility, pilot or exploratory in the title

Cost per patient £2812

454

720

866

1400

569

Is the research question in remit? •Is the research question within the remit of the NIHR programme being applied to?

•If it’s in response to a commission, how do you address the question? •Talk to the programmes concerned or consult the NETSCC or CCF web pages: www.netscc.ac.uk/funding or www.ccf.nihr.ac.uk for advice

Submitting to the right programme • EME – exploratory trials, less pragmatic, phase IIb-III,

efficacy, mechanisms if possible? • HTA – systematic reviews, large multicentre pragmatic trials

or other studies (phase 3-4), effectiveness in the NHS (III-IV) • (HS&DR – organisational, patient experience, qualitative or

other: PHR – nonNHS public health interventions)

• i4i - translation of bright ideas for new high-tech products into methods of prevention, diagnosis and treatment

• PGfAR- £2m for up to 5 years, awards made to NHS bodies • RfPB – max £350k for up to three years • (Natural History, epidemiology, phase I-IIa)...MRC. • Service evaluation- NHS)

HTA programme • The HTA programme offers 3 funding workstreams:

Types of Research

Specific technology assessment

Primary research Feasibility & pilot Evidence synthesis

Who defines the question?

NICE

Researcher

Frequency Per year

Direct referral to On-contract teams

Primary research Evidence synthesis

Theme from HTA programme Question from researcher

Continuous with 3 closing dates

Researcher Led

Primary research Feasibility & pilot Evidence synthesis

HTA programme 3 calls

Clinical evaluation

Themed Calls 1 call

NICE Guidance

Commissioned

EME programme funding opportunities

• Call information available from: www.eme.ac.uk/funding

Translational pull through

Researcher-led

Types of Research

Primary Research; Clinical efficacy of interventions

Primary Research; Clinical efficacy of interventions

Who defines the question?

Researcher

EME programme

Frequency Per year

Continuous with 3 submission deadlines

As required

Is the question important? •The need for the research

– How much will patients or the NHS benefit from the proposed research or healthcare technologies.

– Is there a clear trajectory into patient benefit. – Has the research question been explained clearly

and the importance of topic made (e.g. burden of disease, impact on service / population, gaps in the knowledge identified and how this research will address these gaps)

– Evidence? Patient, specialist support etc – Not just technology in search of a question (“big

scanners”)

Do we get it right?

• Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial OCT 2009

• Effectiveness of H1N1 vaccine for the prevention of pandemic influenza in Scotland, UK: a retrospective observational cohort study 26th June 2012 Lancet Infectious Diseases

• Verteporfin photodynamic therapy for neovascular age-related macular degeneration: cohort study for the UK.

• IVAN, “Blindness prevention drug could save NHS £84.5m, trial

results show” BBC & Guardian

Is the research feasible?

• Is the presentation and/or methods appropriate for the research question?

• Design complexity • Recruitment rate

• Centres (signed up?) • Eligible patients • Patient consent rates • Patient follow-up • Expectations of service providers / patients

• Experience, track record of research team

Consider a pilot (check definition!) Gather as much information as you can to convince of this

The science

•Sample size • Effect size

•Outcomes • Must be appropriate for programme applied to

e.g. HTA patient centred, EME surrogates, i4i healthcare technologies

• Composite measures (e.g. QALYs) or surrogates depending on programmes

• Useful to look at completed or on-going research on the programme websites

The science

•Stage of development of technologies • Especially for complex interventions • Some programmes support developmental or exploratory

studies where there is a clear path to the evaluation • Some programmes supports pilot or feasibility studies

leading to major applications to other NIHR funding streams (e.g RfPB)

•Can include qualitative or quantitative research •Comparators

• Best alternative, treatment as usual, placebos

Costings •Is the research realistically costed and does it offer value-for-money?

•Is the cost to address the disease / health issue in question justified, and does the topic clearly account for the cost requested?

•NB - Costing – we also consider NHS support costs and Excess treatment costs in this, even though we don’t provide them

You want how much?!!

Other advice

•Take advice from experts –Not just technology or clinical experts but research experts

•RCTs and test accuracy studies are DIFFICULT! •Stats, Health economics, trials design/delivery

–Research Design Service –Clinical Trial Units –Get experts on board as co-applicants?

•Engage networks

Other advice 2

•English for mixed audience – Clinical, methodologists, patient and public – Tell the story well for the non - expert – Plain English summary – Follow the application guidance notes.

•Visible headings – (e.g. sample size, outcomes, technologies)

•White space – there should be some (use paragraphs) •Flow diagrams

Feedback from funding boards/committees •Feedback from funding boards at all stages is meant to be helpful to the applicants •Applicants should respond to all areas highlighted as necessary by the funding board

Best places to spot inexperience? Basic! #1 •Inconsistent accounts of planned research •Incorrect or inconsistent numbers e.g. sample size calculations or missing entirely. •Apparent lack of awareness of major or related work in train •Insufficient detail, or muddled detail particularly in the methodology sections – even at full proposal •Gaps in expertise on the research team – even after feedback from funding board

Best places to spot inexperience? Basic #2 •Inadequate detail given on the health issue or demonstrations of benefit to patients •Inadequate detail given on the intervention to be evaluated or the medical device or technology to be developed. •Application has not stuck to programme remit and/or the call •Application has not paid enough attention to board feedback between outline and full proposal •Unrealistic / inaccurate costings (both under and over-costing) •Submissions have not been proof-read

Patient and Public Involvement •Patient and public involvement is of key importance •Researchers need to involve patients and the public during the development and delivery of the research project •Patients and public will be involved at all stages of the assessment process (referees, board members) •Funding boards will explicitly look for evidence of appropriate patient and public involvement

• CTU and network involvement (missing, or token) • Inclusion/exclusion criteria (too narrow) • Identification and numbers of eligible people (too

optimistic) • Consent and numbers consenting (vague; too optimistic) • Follow up rate (unrealistically high or unacceptably low) • Effect size (much too large) • Number and type of sites (too narrow; willingness

asserted)

Best places to spot inexperience? Advanced #1

• Cluster design (but (much) too small ICC) • Cluster design (but no discussion of post randomisation

consent bias) • Multiple arms (but no clear plan for analysis) • Factorial design (but no discussion of interaction) • Data collection (too many measures, too often) • Analysis plan (absent, or uses fraction of data collected) • Outcome measures in unblinded studies (especially

process outcomes that are under patient/clinician control)

Best places to spot inexperience? Advanced #2

Best places to spot inexperience? Advanced #3 • Patient centred outcomes missing (or good reason why

not) • Specification of intervention (vague or unrealistic – or

both) • Delivery of intervention (ditto) • Treatment of population diversity (ditto) • Estimates of time for set up, etc (ditto) • In all the above: any EVIDENCE of feasibility,

acceptability etc?? Any pilot studies? Where did figures come from? Working backwards?

• Assertions regarding behaviour of health care professionals and other staff not employed on the project, for example:

• “GPs will (enter a long list of tasks)….” » ..Oh no they won’t!!!

Best places to spot inexperience? Advanced #4

Take-home messages • Choose your question very carefully.

– Be ambitious – but realistic

• Choose your team well – Delivering clincial research is a professional activity

– get experienced people on board

• Pay a lot of attention to methodology/delivery. – Convince us you can do the research

Final lottery tip

You have to buy a ticket.

Research programmes managed by NIHR CCF • Invention for Innovation Programme (i4i) • Programme Grants for Applied Research

Programme • Programme Development Grants • Research for Innovation, Speculation &

Creativity Programme (RISC) • Research for Patient Benefit Programme

Research programmes managed by NIHR CCF generally to NHS, no FEC

• Invention for Innovation Programme (i4i) • Programme Grants for Applied Research

Programme • Programme Development Grants • Research for Patient Benefit Programme

Programme Grants for Applied Research • Support applied health research to provide evidence to improve

health outcomes in England through promotion of health, prevention of ill health, and optimal disease management (including safety and quality)

• Particular emphasis on conditions causing significant disease burden, where other research funders may not be focused, or there is insufficient funding available

• Support the longer-term development of top quality applied research groups working in the NHS

• Support work whose emphasis is on delivering research findings that will have practical application for the benefit of patients within 3-5 years of programme’s end

• Support health services research, public health research, behavioural research, economic evaluations, and modelling

Programme Grants for Applied Research • Total funding builds to £50m per annum • Programme Director - Professor Adrian Grant • Maximum award £2m for up to five years • Awards made to NHS organisations in England with

subcontracts to academic partners • Two funding rounds per annum • Two stage application process

What makes a successful Programme Grant application? • Excellent track record in applied health research • Necessary breadth and depth in team • Very important research area • Identifiable deliverables within 3-5 years • Ambitious and coherent proposal • Appropriate arrangements for PPI • Identifies and addresses major challenges • Promises excellent value for money • Well written and clearly presented

Programme Development Grants • Designed to enable a research team to undertake preparatory work

that will position it to submit a successful Programme Grant application in a subsequent funding competition

• Programme Development Grants will support: – Evidence synthesis (including modelling) – Selection/development of interventions or outcome measures – Pilot/feasibility studies – Initiation/development of collaborations with methodologists – Convening meetings of the research team

• Awards of £20k - £100k over a period of 6 − 18 months • Successful applicants can submit a full Programme Grant application

without previously submitting an outline application. • No guarantee of Programme Grant award

Research for Patient Benefit Programme • Supports high quality investigator-led research projects

that address issues of importance to the NHS • Proposals are identified by health service staff, and

developed by them with appropriate academic input. • Supports qualitative or quantitative research that could:

– Study the way the NHS services are provided and used – Evaluate whether interventions are effective and provide value

for money – Examine whether alternative means for providing healthcare

would be more effective – Formally assess innovations and developments in healthcare – Pilot or assess feasibility of projects requiring major

applications to other funders

Research for Patient Benefit Programme • National, response-mode project funding programme • Funding building up to £25 million per year • Programme Director - Professor David Armstrong • Maximum award £350k for up to three years • All researchers in the NHS in England can apply • For joint NHS/university applications, funding is

awarded to the NHS partner • 10 Regional Funding Committees • Three funding rounds per year

What makes a successful RfPB application?

• Consulting and involving others – Using local resources – Building appropriate partnerships – Inclusive working with patients

• Keeping the decision criteria in mind – Achieving a convincing research design – Explaining the context for the study – Tackling patient and public involvement – Specifying outcomes for the NHS – Providing a well crafted proposal

• Seek advice from the Research Design Service

Invention for Innovation Programme (i4i)

• Programme aims to support and accelerate the translation of bright ideas for new high-tech products into methods of prevention, diagnosis and treatment.

• Focuses exclusively on funding proposals from academics or companies active in the medical sector.

• Programme Director is Martin Hunt • Four response-mode funding streams • Total funding rising to £13m pa

i4i Funding Streams

• Stream 1 – i4i Feasibility Study – Up to one year investigation to determine whether a piece of prior

basic research or an existing technology can be used to meet a healthcare need, and then to identify the barriers that would need to be overcome before implementation

– Up to £100K available

• Stream 2 - i4i Initial Product Development – Detailed investigation of up to 3 years building on the results of a

completed feasibility assessment to produce a medical device or product through technological improvement or development.

– Provides further evidence of capacity to deliver improved healthcare outcomes and commercial opportunities

– £150-250K available

i4i Funding Streams (2)

• Stream 3 – i4i Commercial Viability Study – Up to one year collaborative study, involving collaboration between

industrial and research partners, to determine whether an innovative use of an existing or emerging product or technology can be used to meet a healthcare need and to identify the barriers that would be need to be overcome.

– Funded projects serve primarily as the first stage of a full collaborative applied research project.

– 75% funding, up to £100K available

• Stream 4 – i4i Collaborative Product Development – Detailed investigation of up to 3 years, involving collaboration

between industrial and research partners, to provide further evidence of the capability to deliver improved healthcare outcomes and commercial opportunity

– Delivers an advanced prototype along with plans for commercial and intellectual property exploitation.

– 50% funding, £100-300K pa available.

Getting innovations into practice

Effectiveness and cost-effectiveness

Basic biomedical research

Translational research

Safety and efficacy

General clinical use

HTA

Horizon-scanning

MRC,

BRCs, i4i

HSDR

EME Specialist commissioning

MRC, Various funders

Appraisal (NICE)

Regulation (MHRA,

IPAC-NICE)

Does it work? Is it safe? Can it be allowed to be done in the NHS? What if it is

done in the NHS? Should it be done in

the NHS - appraisal

The NIHR Research Design Service (RDS) supports

researchers to develop and design high quality research proposals for submission to

NIHR and other national, peer-reviewed funding competitions for applied health or social care

research.

Prioritisation Panels

• Clinicians and patients

• NHS focused

• Needs-led

Prioritisation Group

• Initial look at feasibility and value of question

• Portfolio balancing

Commissioning Board

• Academics • Focused on

the deliverability and value for money of proposals

HTA programme: adding value

DH

research quality of proposals, host and team; VfM