Review of current core capacity of UKCRC Registered ... · PDF fileRegistered Clinical Trials...

Review of current core capacity of UKCRCRegistered Clinical Trials Units and future

resource requirements for the developmentand delivery of academic-led, late phase,

randomised controlled trials across the UK

Prepared by:Helen Howard (UKCRN), Julia Brown (UKCRN/Clinical Trials Research Unit, Leeds),& Helen Meadows (UKCRN/CR UK & UCL Cancer Trials Centre) in consultation with

the UKCRC Registered Clinical Trials Units

On behalf of the UKCRC Clinical Trials Units Oversight Group:

Angela Cooper (MRC), Peter Davidson (NIHR HTA Programme), Rebecca Hodges(UKCRC), Rury Holman (Diabetes CTU, Oxford), Catherine Johns (DH), Kate Law

(Cancer Research UK), Gareth Lewis (Pfizer), Elaine McColl (Newcastle CTU), JohnNorrie (Centre for Healthcare Randomised Trials, Aberdeen), Liz Philpots (AMRC),

Craig Stevenson (Novartis), Janet Valentine (UKCRC)

November 2008

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TABLE OF CONTENTS

LIST OF TABLES I

EXECUTIVE SUMMARY III

1. INTRODUCTION 1

1.1 Background 1

1.2 Scope of the Project 2

2. REVIEW OF CURRENT REGISTERED CTU CAPACITY 4

2.1 Current Distribution of Registered CTUs and Disease/Health ResearchInterest 4

2.2 Core Resources in CTUs 5

2.3 Benefits of Core Funding 10

2.4 Current Core Resources in UKCRC Registered CTUs 14

2.5 Current level of RCT activity 23

3. MODELLING CTU CORE CAPACITY REQUIREMENTS 27

3.1 Overview of model developed for 2005 NCRI review 27

3.2 Review of NCRI CTU Capacity Model and Adjustments for the CurrentProject 32

3.3 Application of adjusted model to current level of RCT activity in registeredCTUs 36

4 ESTIMATING ADDITIONAL FUTURE CTU CORE RESOURCEREQUIREMENTS 38

4.1 Anticipated change in number of RCTs in UKCRN Clinical ResearchPortfolio 38

4.2 Anticipated change in the proportion of UKCRN Clinical ResearchPortfolio RCTs managed by the Registered CTUs 39

4.3 Estimated CTU Core Resources Required to Support Additional FutureRCT Activity 39

5 DISCUSSION 42

5.1 Review of Current and Future Registered CTU Capacity Requirements 42

5.2 Considerations for the Expansion of Core CTU Resources 44

5.3 Concluding remarks 48

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APPENDIX 1: UKCRC CTU Registration 49

APPENDIX 2: Geographical distribution of all registered CTUs 52

APPENDIX 3: Geographical distribution of UKCRC Registered CTUs according todisease research interest 53

APPENDIX 4: List of other sources of CTU core staff funding 65

APPENDIX 5: List of other CTU staff roles 65

APPENDIX 6: List of organisations funding five or fewer UKCRN Portfolio RCTs 66

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LIST OF TABLES

Table 1. Summary of disease/health research interests of the 40 RegisteredCTUs

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Table 2: Summary of change in the RCT portfolio of NCRI Accredited CTUsbetween 2006 and 2008

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Table 3: Summary of Cancer Research UK project grant applications betweenJanuary 2006 and January 2008 by NCRI Accredited CTUs.

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Table 4. Summary of formal core funding provided to registered CTUs 15

Table 5: Estimated current distribution of formal core funded salariesaccording to funder and disease/health care need research area.

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Table 6: Summary of distribution of current registered CTU resources andformal core funding by disease/health care need research area.

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Table 7: Summary of all core funded staff in the 40 registered CTUs andsource of funding.

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Table 8. Summary of salary data for core CTU staff roles collated fromregistered CTUs (excluding on-costs at 20%)

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Table 9. Current salary funding of core staff in the 40 registered CTUs(including on-costs at 20% but excluding overhead costs)

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Table 10. Stability of core CTU staff in registered CTUs determined byprobability of renewal of salary funding.

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Table 11. Summary of stability of current core staff in registered CTUs 23

Table 12: Breakdown of the source of project grant funding for 630 RCTseligible for inclusion in the UKCRN Clinical Research Portfolio identified fromthe UKCRN Portfolio database and CTU registration application forms.

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Table 13. Estimates of the core staff requirements (WTE) for the developmentand delivery of one academic-led, late phase cancer RCT.

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Table 14: Estimates used in the current project of the core staff requirements(WTE) for the development and delivery of one academic-led, late phase RCT.

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Table 15: Estimate of CTU core resources (WTE) required to support thecurrent level of activity at steady state.

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Table 16: Summary of the anticipated change in number of clinical trialsfunded by key UKCRN Portfolio funders over the next 3 years

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Table 17: Anticipated number of UKCRN Portfolio RCTs starting in next 3years and number coordinated by registered CTUs according to differentscenarios where the proportion of UKCRN Portfolio RCTs involving theregistered CTUs is varied.

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Table 18: Estimated additional core resource requirements per year tosupport additional RCT activity (i.e. over current level of activity) and estimatedcosts (including 20% on-costs, but excluding overheads).

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Table 19: Potential capacity of the registered CTUs to expand staff numberswithin current accommodation.

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EXECUTIVE SUMMARY

Introduction

The UK clinical research environment has undergone significant changes over thelast few years, with the overall aim of increasing the quality and quantity of clinicalresearch and ultimately improving health. The strengthening of the research capacityof the NHS through establishment of the clinical research networks, and streamliningof the systems and processes underpinning clinical research have been paralleled byinitiatives such as the creation of Clinical Studies Groups to oversee the strategicdevelopment of research portfolios in key disease areas, engagement of patients andthe public to ensure the programme of clinical research in the UK is focused onmeeting their needs, and the development of closer working links between allstakeholders and clinical research funders. This whole system approach to thedevelopment and coordination of the UK’s clinical research environment is essentialto ensure that the impact of the changes and the associated increase in funding forclinical research is fully realised in terms of patient benefit.

The unprecedented levels of investment in developing and strengthening clinicalresearch infrastructure in the UK over recent years has been accompanied by anexpansion in the portfolio of clinical research projects reflecting significant increasesin funding for academic-led research. Large-scale, randomised controlled trials(RCTs) in particular, are pivotal in providing reliable information on the clinicalbenefits and risks and the cost effectiveness of new interventions. Late phase RCTsoften involve hundreds or thousands of patients, making their design, coordination,monitoring, and analysis a complex process, particularly in the case of clinical trialsof investigational medicinal products (CTIMPs) where stringent regulations apply.Clinical trials units (CTUs) play a key role in providing the dedicated expertise andsupport necessary for the design, development, management, analysis andpublication of high quality clinical trials. CTUs provide this expertise through wellestablished multidisciplinary teams which typically include clinicians, statisticians, trialmanagers, data managers, and epidemiologists. These teams provide the fullspectrum of functions required for RCT design, coordination, and analysis, including:

systematic literature review trial design expertise clinical expertise statistical expertise (e.g. sample size calculations, analysis methods and

plans) expertise in qualitative research and health economics coordination of consultation with clinical research networks, collaborative

groups, industry, patients and public study feasibility assessment protocol development development of grant proposals preparation of ethical and any relevant regulatory submissions database design, development, and validation clinical site identification and set-up procurement and management of trial supplies data management and monitoring surveillance and monitoring of protocol compliance pharmacovigilance and safety reporting

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trial oversight (e.g. organisation of trial steering committees (TSC) and datamonitoring committees (DMC))

interim and final data analyses preparation of reports and dissemination of results

The complex nature of the work undertaken by CTUs is underpinned by robustsystems for quality assurance, data management and business processes which inturn are supported by other dedicated CTU staff including programmers andinformation systems staff, quality assurance staff, business managers, andadministrative staff.

Funders of clinical trials are increasingly looking for evidence that investigators haveinvolved CTU expertise in the development of research proposals, and intend tocontinue working with the CTU on the delivery of the project (as an indication ofexpert input and quality assurance). The demand for expertise within CTUs istherefore expected to increase as the increased investment in UK clinical researchenvironment takes effect. In order to ensure that CTUs can keep up with thisdemand, it is essential that the existing capacity of this resource is assessed and theneed for any further development and strengthening identified and quantified.

With the increase in clinical research funding which followed the Cooksey review ofhealth research funding [1], it is essential that sufficient high quality CTU capacityexists in the UK to underpin and support the expansion of the UK Clinical ResearchNetwork (UKCRN) Clinical Research Portfolio, particularly with regard to late phaseRCTs. The UK Clinical Research Collaboration (UKCRC) Board acknowledged thecritical role of CTUs in supporting the development and delivery of high quality RCTswhen it announced the UKCRC CTU Registration Process in 2007. Following thefirst call for UKCRC CTU Registration in 2007, a total of 40 of the 57 UK CTUs whichapplied were awarded UKCRC Registration status (26 with full registration, and 14with provisional).

In order to obtain a more detailed picture of the current capacity in the UKCRCRegistered CTUs, a project has been undertaken by UKCRN on behalf of theUKCRC Board with the following objectives:

1. to understand where the current high quality CTU capacity exists (in terms ofgeography and disease/health research focus)

2. to assess how much CTU capacity currently exists

3. to assess how stable the current CTU capacity is

4. to evaluate whether there are geographical or disease gaps in the existingCTU capacity to respond to requirements over the next 3 years

5. to estimate how much CTU capacity is needed to support anticipated activityin the UKCRN Clinical Research Portfolio over the next 3 years

1Sir David Cooksey (2006) A review of UK health research funding.

http://www.hm-treasury.gov.uk/media/4/A/pbr06_cooksey_final_report_636.pdf

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Scope of the current project

The Clinical Research Networks were set up to support RCTs and other welldesigned studies and indeed most CTUs undertake RCTs as well as other types ofresearch such as meta-analyses, observational epidemiological studies,methodological and qualitative research as well as RCTs. However, the currentproject has specifically focused on the core staff resources within the 40 registeredCTUs to support large, late phase RCTs since the number of RCTs within theUKCRN Clinical Research Portfolio is expected to increase substantially over thenext 3 years.

Core staff are defined as those posts within the CTU which are funded independentlyof specific research grants. Current funding sources for core staff are varied and forthe purpose of this report have been assigned to two categories:

1. formal core funding (i.e. funding awarded specifically to support the CTU’score activities and infrastructure as a whole rather than a particular project orindividual)

2. non-formal core funding (i.e. funding not awarded specifically to support theCTU’s core activities and infrastructure as a whole, but which may be used tosupport individuals carrying out core activities (e.g. individual fellowships ortenures; retained funds/overheads)).

Typically, core staff are responsible for activities which include:

ongoing oversight and governance of trials through all stages of development,management and analysis/publication

maintenance of non-project-specific CTU systems and processes (e.g. qualityassurance; data management; business and financial)

management and strategic development of the CTU

methodological developments

training, supervision, and professional development of CTU staff

These activities are fundamental to the stability and quality of work which CTUsundertake, and incorporate the typical roles of many senior CTU staff. Unless a CTUreceives a formal core grant, the funding for core staff often has to be found from anumber of different sources which are less likely to offer secure long term support.This impacts on the CTU’s ability to retain vital expertise and experience and istherefore also critical to the quality and delivery of the UKCRN Clinical ResearchPortfolio. This has been evidenced in the case of cancer research where coreresources in some cancer CTUs were strengthened through additional investmentfrom Cancer Research UK following a similar report on the core capacity of cancerCTUs for the National Cancer Research Institute (NCRI) in 2005 [2]. Since receivingadditional funding in 2006, those CTUs have reported a greater increase in the sizeof their cancer RCT portfolio compared to those CTUs which did not receive furthercore funding, and also have a higher overall rate of success in securing funding forcancer trials.

2 Stead ML & Meade AM (2005) Costs of the National Cancer Clinical Trials Portfolio Part 2: CoreFunding Resource Requirements (for the Development and Management of Phase III CancerRandomised Controlled Trials)

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Review of Current Registered CTU Capacity

The review first addressed the availability of registered CTUs in key disease/healthresearch areas corresponding to the UKCRC Health Research Categories [3] plusClinical Research Network topic areas, and their geographical distribution. Thedisease/health research interests of the registered CTUs currently cover all but onearea (none currently undertake ear research). The number of CTUs in some diseaseareas is small (e.g. eye; congenital disorders; injuries and accidents) and thereforegeographical coverage is limited, but the number of CTUs appears to be consistentwith the size of the national portfolio for those areas (see Table 6). Since most of theregistered CTUs are willing to work remotely with investigators, the more limitedgeographical distribution of CTUs catering for these smaller disease portfolios shouldnot present issues.

Current core resources in Registered CTUs and their stability

The review also explored the capacity of the registered CTUs to support both thecurrent and future levels of RCTs in the UKCRN Clinical Research Portfolio byreviewing the current numbers and stability of support for core staff within theregistered CTUs.

There are currently 516 core staff within the 40 registered CTUs (Table 7), includingresearch staff such as CTU directors or programme leaders, statisticians, trialmanagement staff, as well as support staff such as those involved in qualityassurance, database and information systems, and financial/contracting roles.

Information has been gathered from the registered CTUs relating to the source andstability of funding for their core staff (in terms of expiry and likelihood of renewal).Only 22 registered CTUs currently receive any formal core funding which supportsapproximately 55% of core the staff posts amongst the 40 registered CTUs. Thefunding for the remaining core posts is provided via non-formal core funding (seeTable 7).

In terms of the stability of existing core posts, the data collected suggest that thefunding for approximately 64% of current core staff is considered to have a highlikelihood of renewal. This offers distinct advantages to CTUs by affording security tothe core staff, which in turn allows CTUs to maintain quality and to develop longterms plans and strategies for the development of the unit. Approximately 75% ofthese “secure” core posts are funded from formal core CTU grants.

Approximately 33 (6%) further core posts are not subject to expiry (e.g. where staffare tenured by host institutions) and may therefore be regarded as “secure”.However, whilst these posts may be secure with regard to the member of staffconcerned, they are often not committed specifically to CTU activity and may nottherefore be secure in terms of providing specific CTU core resources.

The renewal of funding for approximately 128 (25%) current core posts is consideredunlikely or uncertain, of which 93 are from non-formal core funding sources due toexpire over the next 4 years (i.e. by 2012). Information about the stability of fundingfor 27 (5%) of core posts was not provided.

3 UKCRC Health Research Classification Systemhttp://www.ukcrc.org/PDF/Health%20Research%20Classification%20System%20October%202007.pdf

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The data gathered from the registered CTUs therefore suggest that at least 128 ofthe 516 current core posts (at all levels) are not secure but could be stabilisedthrough new or extended formal core grants. The number may be considerablyhigher if those posts where information on stability of funding is lacking, as well asthose with no fixed expiry (generally more senior staff) which do not necessarilytranslate to formalised core CTU resources, are also considered as potentially non-secure.

CTU core capacity in relation to current number of RCTs in the UKCRNClinical Research Portfolio

Current core CTU capacity has been approached by relating the current numbers ofcore staff to both the current level of RCT activity and to anticipated increases in thenumber of new RCTs starting each over the next 3 years. Estimates of requiredcapacity were based on an adapted version of the model used for the NCRI CTUcapacity project (see Table 14) which considers the core staff resources required ateach stage of the RCT life-cycle (i.e. development of grant proposal, post-grantdevelopment, recruitment of patients, active follow-up, and analysis and publicationof data). These estimates can then be used as a basis for estimating the totalnational core staff resources required to support a given number of RCTs. In allcases, estimates derived from the model are presented as ranges to take intoaccount the core resources needed in a variety of scenarios where the volume ofoutline and full grant applications are varied. The variations used reflect a range ofcurrent clinical trial grant success rates based on data from the major project funders(namely, MRC, NIHR Health Technology Assessment programme, and CancerResearch UK).

With regard to current levels of RCT activity, it is estimated that there areapproximately 709 ongoing late phase RCTs (i.e. in set-up, open to recruitment, or inactive follow-up) in the UK which are eligible for inclusion in the UKCRN Portfolio,and that approximately 131 new RCTs eligible for the UKCRN Portfolio are launchedper year (based on data for 2007). Registered CTUs are estimated to manageapproximately 55% of the current RCTs in the UKCRN Clinical Research Portfolio(i.e. 382 of ongoing and 72 new RCTs per year).

Using the model, it is estimated that between 576 and 738 core CTU staff arerequired to optimally support 55% of current levels of ongoing and new RCT activityin the UKCRN Portfolio. This suggests a current shortfall of between 60 and 222core staff relative to the actual number of core staff in place (i.e. 516). Thisshortfall is mainly in the senior/clinical staff categories and it is likely that this iscurrently being met by project funded CTU staff.

CTU core capacity in relation to future number of RCTs in the UKCRNClinical Research Portfolio

Based on information from major UK funders, the number of new RCTs starting peryear is expected to increase from 131 in 2007 to around 198 by 2011. If registeredCTUs maintain the proportion of UKCRN Portfolio RCTs which they manage(approximately 55%), they would expect to be involved in launching 109 new RCTseach year (plus ongoing RCTs). However, since it is becoming increasingly commonfor funders to request confirmation from investigators that they have obtained expertinput into the design of their trials and have collaborative arrangements in place to

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work with CTUs on the management of new RCTs, it is expected that they will beinvolved in a greater proportion of RCTs as new investigators seek theircollaboration, particularly in the case of more complex RCTs, such as large scalestudies or CTIMPs. Therefore, a number of future scenarios have been modelledwhich consider a variety of grant application success rates along with variations inthe proportion (i.e. 55% - 70%) of the RCTs in the UKCRN Portfolio which theregistered CTUs could manage as activity expands over the next 3 years (see Tables17 and 18).

A realistic goal is for the registered CTUs to support at least 65% of new RCTsstarting in the UKCRN Portfolio by 2011. This would involve the registered CTUs inlaunching an extra 57 new RCTs each year by 2011 (i.e. over and above the currentlevel of 72 per year), and eventually the management of an extra 371 ongoing RCTsper year (this includes RCTs in start-up, recruitment, follow-up and analysis) by 2017.It is estimated that this would require between 394 and 436 additional core CTUstaff by 2017 (see Table 18). It is important to note that this estimate does not takeinto account the lack of stability of a significant proportion of current core staff postsin registered CTUs or the estimated current shortfall in core posts (as discussedabove). The range in the estimated additional core resources required reflects thedifferent grant applications success rates used in the model which ranged from a60% success rate for both outline and full grant applications (36% overall), to a 50%success rate for both outline and full grant applications (25% overall). The latterscenario is a realistic representation of current grant success rates, but it isanticipated that with optimal core resources in place, grant success rates wouldmove towards the former, and therefore the number of additional core staff requiredwould be closer to the lower figure (i.e. 394).

It is difficult to comment on whether this expansion in core CTU resources should befocused within particular disease/health research areas as the anticipated increase inRCT funding from the main funders over the next 3 years is not associated with aspecific disease. The possible exception to this is the musculoskeletal researchportfolio where a modest increase is expected.

Therefore, if the registered CTUs are to aim to effectively support 65% of RCTs in theUKCRN Portfolio by 2011 onwards, the following issues would need to be addressed:

1. the estimated required expansion of between 394 and 436 additional corestaff posts to support the additional trials by 2017;

2. the estimated 25% of existing core staff posts whose funding is not secure;

3. the estimated shortfall of between 60 and 222 core staff posts needed tooptimally support the current level of RCT activity in the registered CTUs.

The National Institute for Heath Research (NIHR), through the HTA programme, hasrecently committed some funding to strengthen the capacity of CTUs in Englandthrough a system of rolling support contracts whereby successful CTUs receive‘priming funding’ prior to project grant applications. A proportion of this funding(80%) is then offset against subsequent successful NIHR project grants awarded tothe CTU. A total of £3.5m was awarded across 17 registered CTUs following the firstcall for this initiative in June 2008; it is anticipated that, collectively, the CTUspotentially retain approximately £700k of this per annum for core support.

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Expansion of CTU core resources

The potential options for delivering the required increase in CTU core resourcerequirements include:

1. Expansion within registered CTUsFocusing the increase in core CTU staff in the UK within registered CTUs presents anumber of advantages. These include:

existing infrastructure and systems are already in place (e.g. appropriateaccommodation for staff and data storage; QA systems; data and informationmanagement systems)

experienced senior staff in place to train and develop new expertise

track record of developing and managing RCTs

well established collaborative relationships with other research groups (e.g.health economics; research networks)

Information from the registered CTUs suggests that many have the capacity toexpand their staff numbers in their existing accommodation. Collectively, it isestimated that the registered CTUs could accommodate at least 206 additional newstaff (this does not take into account further potential expansion which might beaccommodated through acquisition of additional office space). It is also worth notingthat a further round of UKCRC CTU Registration is planned for 2009 and it isanticipated that the number of registered CTUs will increase.

2. Expansion within existing non-registered CTUsEffective expansion of core staff in non-registered CTUs is, in most cases, likely torequire greater investment than in registered CTUs due to the need to ensure thatCTU infrastructure systems are also adequate to meet the requirements ofmanaging a portfolio of large scale RCTs. However, investment in established non-registered CTUs provides the advantage of allowing these CTUs to work towards fullUKCRC registration status. Any investment in core infrastructure of non-registeredCTUs could carry the condition that UKCRC registration must be achieved within aspecified timeframe, and that they should work closely in a mentoring arrangementwith a registered CTU.

3. Creation of new CTUsInvestment in existing CTUs (whether registered or not) presents a more costeffective option than creating new CTUs. New accommodation must be identifiedfor CTUs, as well as procurement of database systems and equipment. These costswould be over and above those considered in the current project. Moreover, anentire CTU team would have to be established and time taken to establish theexpertise for the full functions required of the CTU. Establishing new CTUs mustalso take into account the level of engagement and support from potential hostinstitutions. Any investment in new CTUs could again carry the condition thatUKCRC registration must be achieved within a specified timeframe, and that theyshould work closely in a mentoring arrangement with a registered CTU.

4. Utilise expertise within other organisationsThere may also be scope to utilise expertise within other organisations, for exampleNIHR Research Design Services (RDS), NIHR Collaborations for Leadership inApplied Health Research and Care (CLAHRC), and MRC Hubs for TrialsMethodology Research (HTMR). However, whilst the expertise of CTUs covers the

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full spectrum of clinical trials development and delivery (covering trial design,coordination, data management and analysis and publication), the remit of the RDSis specific, focusing on the development and design of high quality researchproposals, whilst CLAHRCs focus on implementation research and HTMRs have aspecific remit of methodological research.

The limited availability of expertise in clinical trial design, conduct and analysisnationally has already caused difficulties in recruitment to Registered CTUs. Creatingnew CTUs would exacerbate this by distributing the existing expertise more thinly andcould compromise the function of established CTUs by depleting them of key seniorstaff, whilst failing to provide a critical mass of expert and experienced staff to allow newCTUs to establish themselves within a realistic timeframe. Investment in the expansionof existing CTUs would facilitate the development of new expertise as these CTUs willbe well placed to develop new staff and oversee progression of existing staff into moresenior roles. In the medium to longer term, having ensured adequate expansion ofexpertise in established CTUs, the distribution of expertise to less developed or newCTUs will be more feasible and less likely to have a negative impact on the capacity ofestablished CTUs. However, in order to address the shortage of expertise, acomprehensive workforce development strategy, similar to those developed under theauspices of UKCRC for other research professionals such as doctors and dentists andresearch nurses, is required for CTU staff at all levels, from senior clinicians,epidemiologists, statisticians and trial management staff to quality assurance managersand information systems staff.

Delivery of the necessary investment in core CTU resources is likely to be approachedby funders in different ways. This may be influenced by funders’ existing budgetallocations and the balance between the funding available to CTUs via core grantsversus project grants. If funders do not have the scope to commit significant amounts offunding to formal core infrastructure grants, they may be able to contribute to theexpansion of CTU core resources by increasing project grant funding to include anelement which is specific to core activity.

Finally, CTU host institutions stand to gain considerable income via overheads/FEC onboth the core grants and project grants to their CTUs. Amongst the 40 registered CTUs,32 are hosted by Higher Educations Institutions (HEIs). Therefore, HEIs as a groupneed to be fully engaged in discussions regarding the key role CTUs play in leading andsupporting clinical research in the UK so that they recognise the potential benefit ofstabilising CTUs not least because of the additional project funding that is likely to beobtained over the longer term. By working with CTUs and funders which provideoverhead costs/FEC, it is hoped that business models could be developed in HEIs toensure that monies obtained through overheads/FEC on CTU grants are directedtowards the development and support of CTU activity within their organisations.

Summary

This review has considered current capacity and predicted requirements in the UK todevelop and deliver academic-led, late phase RCTs in the UKCRN Clinical ResearchPortfolio. It has focused specifically on the core resources in the 40 UKCRC RegisteredCTUs, and their capacity to provide the expertise to support the development andmanagement of the current level of RCTs in the UKCRN Clinical Research Portfolio andthe planned expansion of this activity over the next 3 years.

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The role of CTUs within the evolving UK clinical research environment will becomeincreasingly important over the next few years to ensure that large, complex studiessuch as RCTs are appropriately designed and effectively coordinated.

Whilst the current disease/health research interests of the registered CTUs appears tobe well distributed, both geographically and in relation to the balance of RCTs within thecurrent UKCRN Clinical Research Portfolio, the current core staff resources in theregistered CTUs appears to be sub-optimal in relation to the number of RCTs theseCTUs are involved in coordinating. Furthermore, a significant proportion of current coreCTU resources are considered potentially unstable. These core CTU resources areexpected to be further stretched by the anticipated expansion of RCTs in the UKCRNPortfolio over the next 3 years.

In order for CTUs to effectively meet current and future demand for their expertise,existing CTU core resources need to be strengthened and expanded in parallel with theplanned increase in the number of RCTs in the UKCRN Clinical Research Portfolio.Without this expansion, there is a clear risk that, despite the recent substantialinvestment in project funding and NHS clinical research infrastructure, new, high qualityRCTs will not be developed at the rate expected and may fail to be successfullydelivered due to lack of expert oversight. This review was set up to assess the likelydemands on the registered CTUs over the next 3 years and provides the data forfunders to consider what action is needed to underpin the expansion of CTU activityrequired to support the increase in clinical trials.

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1. INTRODUCTION

1.1 BackgroundClinical research in the UK is currently undergoing extensive expansion reflectingunprecedented investment. The last few years has seen the roll out of the UK ClinicalResearch Network (UKCRN) which has been established to increase the ability andcapacity of the NHS to support high quality clinical research across the full spectrum ofdisease and healthcare need. This has been paralleled by increased grant funding fromkey funders. Given the increased level of investment in clinical research and theattendant increase in research activity this is generating, there is a clear need to ensurethe UK maintains the capacity and expertise to ensure studies are designed andsubsequently coordinated and analysed to the highest standards, as well as ensuringreliable and timely completion of studies and dissemination of results.

Many of the studies contained in the UKCRN Clinical Research Portfolio are large,multi-centre, randomised controlled trials (RCTs) which are pivotal in providing reliableanswers about the clinical benefits and risks and the cost effectiveness of newtherapeutic interventions. The design and coordination of this type of study is complexand requires dedicated expertise, particularly in the case of clinical trials ofinvestigational medicinal products (CTIMPs) where stringent regulations apply. Clinicaltrials units (CTUs) offer such expertise through established multidisciplinary teamswhich typically include clinicians, statisticians, trial managers, data managers, andepidemiologists. These teams provide the full spectrum of functions required for RCTdesign, coordination, and analysis, including:

systematic literature review trial design expertise clinical expertise statistical expertise (e.g. sample size calculations, analysis methods and plans) expertise in qualitative research and health economics coordination of consultation with clinical research networks, collaborative groups,

industry, patients and public study feasibility assessment protocol development development of grant proposals preparation of ethical and any relevant regulatory submissions database design, development, and validation clinical site identification and set-up procurement and management of trial supplies data management and monitoring surveillance and monitoring of protocol compliance pharmacovigilance and safety reporting trial oversight (e.g. organisation of trial steering committees (TSC) and data

monitoring committees (DMC)) interim and final data analyses preparation of reports and dissemination of results

The complex nature of the work undertaken by CTUs is underpinned by robust systemsfor quality assurance, data management and business processes which in turn aresupported by other dedicated CTU staff including programmers and information systemsstaff, quality assurance staff, business managers, and administrative staff.

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Funders of clinical research are increasingly looking for evidence (as an indication ofexpert input and quality assurance) that investigators have involved CTU expertise inthe development of clinical research proposals submitted to them and intend to continueworking with the CTU on the delivery of the project. This is particularly true for morecomplex projects such as large late phase RCTs. As a consequence, there is anincreasing burden of responsibility on registered CTUs to provide expertise and supportfor this type of study which carries considerable capacity and resource implications forthese CTUs.

In order to assess the capacity of existing CTUs to respond to the increased clinicalresearch activity, and inform research funders of the current CTU capacity in the UK, aproject has been undertaken to establish the current CTU capacity with the followingobjectives:

1. to understand where the current high quality CTU capacity exists (in terms ofgeography and disease/health research focus)

2. to assess how much CTU capacity currently exists

3. to assess how stable the current CTU capacity is

4. to evaluate whether there are geographical or disease gaps in the existing CTUcapacity to respond to requirements over the next 3 years

5. to estimate how much CTU capacity is needed to support anticipated activity inthe UKCRN Clinical Research Portfolio over the next 3 years

1.1.1 UKCRC CTU Registration ProcessThe UKCRC Board acknowledged the critical role of CTUs in supporting thedevelopment and delivery of high quality RCTs which are eligible for inclusion in theUKCRN Clinical Research Portfolio when it established the UKCRC Clinical Trials Unit(CTU) Registration Process in 2007. The aim of this process was to identify high qualityCTU resources within the UK able to underpin and support the expansion of the UKCRNClinical Research Portfolio. As far as we are aware, almost all established CTUs able tooffer the full range of clinical trial functions submitted an application for registration and,following the first call for registration, a total of 40 UK CTUs were registered: 26 with fulland 14 with provisional registration (see Appendix 1).

1.2 Scope of the Project

1.2.1 Type of CTU consideredThe NIHR Coordinating Centre for Research Capacity Development (NIHR CCRCD)review of clinical trials capacity in 2006 [4] identified approximately 90 organisationsperforming CTU functions in the UK. However, the term ‘clinical trials unit’ wasinterpreted variably and organisations which perform some aspects of clinical trialdesign, coordination, and analysis were included, as well as those performing all. CTUsvary widely in their experience and the extent of the expertise and the functions theyundertake. For the purpose of this project, consideration of CTU capacity focuses onthose CTUs which have the full spectrum of expertise required to take on overallresponsibility for all aspects of the design, conduct (i.e. the central coordination and

4 Edwards A & Lilford RJ The National Clinical Trials Capacity Review Final Reporthttp://www.nccrcd.nhs.uk/rcdinfrastructure/CTCapacityReview.pdf

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management rather than conduct at participating clinical sites), and analysis of latephase RCTs, from concept to publication.

This project focuses specifically on the current capacity of the 40 registered CTUs (i.e.both fully and provisionally registered) which have been judged by an international panelas having the experience and expertise to lead the development and delivery of highquality, large late phase studies.

1.2.2 Type of study consideredThe research activities of the registered CTUs are varied and complex. Collectively,registered CTU activity comprises a whole array of research including epidemiologicalstudies, qualitative research, health economics, experimental medicine, early phaseclinical trials, and methodological research, as well as large scale, late phase RCTs.The CTU resources required for the development and delivery of these different types ofresearch can vary considerably. In the interest of simplicity, the current project focusesspecifically on the capacity of the registered CTUs to support large late phase RCTs.The rationale for this is that the support of such studies was a key driver for theimplementation of the clinical research networks. Furthermore, with continuedinvestment over the next few years, the number of RCTs within the UKCRN ClinicalResearch Portfolio is expected to increase further.

1.2.3 CTU roles consideredIt is recognised that a variety of roles within registered CTUs can be core-funded.However, since the focus of the current project is the capacity for large scale RCTs, itfollows that the CTU core roles which have been analysed in the current project concernonly those that contribute to the development, delivery, and support of RCTs. The rolesconsidered in the current project therefore include core-funded research staff performingin roles such as programme leads (including clinicians), statisticians, and senior trialmanagers, and core-funded support staff roles in IT, quality assurance, and businessmanagement. However, it is recognised that various types of staff may be involved inperforming these roles (i.e. not necessarily those carrying the role titles listed above asterminology varies across CTUs), and this may include, for example, research nursesand epidemiologists. Further details regarding the core staff roles analysed areprovided in section 4.1.2.

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2. REVIEW OF CURRENT REGISTERED CTU CAPACITY

The first call for UKCRC CTU Registration in 2007 attracted a total of 57 applications.Applications were invited from CTUs which are responsible for coordinating multi-centreclinical trials and other well-designed studies. Two levels of registration were awarded:full and provisional. Provisional registration was awarded to CTUs that did not meet thecriteria for full registration, but could demonstrate that that they were working towardspossessing sufficient experience and expertise to gain full registration status (as judgedagainst the criteria for provisional registration).

A total of 40 CTUs were registered: 26 with full registration and 14 with provisional. Alist of these units is provided in Appendix 1 and their geographical distribution is shownin Appendix 2.

2.1 Current Distribution of Registered CTUs and Disease/HealthResearch Interest

Registered CTUs were asked to indicate their research interests with regard todisease/health care need, according to the Health Research Categories developed byUKCRC [5] plus additional categories corresponding to the priority diseases covered bythe clinical research networks where these were not specifically represented. Table 1summarises the number of registered CTUs involved in developing and running clinicaltrials in each of these disease categories and the geographical distribution of registeredCTUs with interests in each disease area is presented in Appendix 3.

5 UKCRC Health Research Classification Systemhttp://www.ukcrc.org/PDF/Health%20Research%20Classification%20System%20October%202007.pdf

5

Table 1. Summary of disease/health research interests of the 40 Registered CTUs

Research Area No. of FullyRegistered CTUs

No. of ProvisionallyRegistered CTUs

Total no. ofRegistered CTUs

Blood 4 2 6

Cancer 22 2 24

Cardiovascular 10 5 15

Congenital Disorders 1 0 1

Dementias &NeurodegenerativeDisease

8 1 9

Diabetes 8 5 13

Ear 0 0 0

Eye 1 2 3

Generic HealthRelevance

2 2 4

Infection 4 5 9

Inflammation &Immune System

3 2 5

Injuries and Accidents 2 2 4

Medicines for Children 7 7 14

Mental Health 10 5 15

Metabolic & Endocrine 5 1 6

Musculoskeletal 10 5 16

Neurology 7 3 10

Oral & Gastrointestinal 10 2 12

Primary Care 11 5 16

Renal & Urogenital 3 0 3

Reproductive &Childbirth

7 2 9

Respiratory 7 4 11

Skin 4 3 7

Stroke 6 4 10

Other 5 2 7

2.2 Core Resources in CTUs

2.2.1 Core funding and role of core staff

All registered CTUs have or, in the case of provisionally registered units, are in theprocess of establishing, a portfolio of RCTs. Therefore, at any given time, there areseveral RCTs running in parallel at different stages within the RCT life cycle. Thispresents a complex scenario within CTUs, placing competing demands on staff timeand expertise. In addition to developing and managing a portfolio of RCTs, these CTUsmust also identify resources to address other areas of activity which are crucial to theongoing development of the CTU (see below).

Typically, clinical trial project grants will cover the specific running costs of the clinicaltrial which includes salaries of those CTU staff who are specifically focussed on the set-up, management, and analysis of the study. However, the complexity and duration ofRCTs calls on continuous input from CTU staff who are not focussed on specific

6

projects and therefore not funded via project grants, but who are responsible for coreCTU activities which include:

ongoing oversight and governance of trials through all stages of development,management and analysis/publication

maintenance of non-project specific CTU systems and processes (e.g. qualityassurance; data management; business and financial)

management and strategic development of the CTU methodological development training and professional development

These activities are fundamental to the stability and quality of work which CTUsundertake. However, since they are not directly associated with any specific project,individual project grants rarely incorporate funding which contributes to the cost of theseactivities. Project grant funding also fails to take into account the significant and oftenintensive contributions of CTU staff during the developmental stages of projects prior tothe award of specific funding, as well as ongoing contributions during the RCT life cyclewhich are not attributable to specific trial grants (e.g. long term follow-up, updatingsystematic reviews, further data analysis, cross trial analyses).

Without stable core funding for key staff, particularly at a senior level, much of theexpertise and essential functions within CTUs is supported through non-CTU specificfunding. Typical CTU activities which are generally beyond the scope of project grantfunding are outlined below.

Development of new trialsThe development of new trials is an intensive process. In the case of RCTs this processusually takes several months and often over a year due to the complexity and the needfor input from a wide range of expertise. Given the expertise within CTUs and thedemand for this, it is to be expected that the development of several new proposals willbe ongoing at any given time and will constitute a significant proportion of the CTU’score activity. However, this activity precedes the award of grants and is rarely, if ever,acknowledged within project grant awards. Furthermore, the grant award review is acompetitive process carrying no guarantee of eventual funding. This highlights an issuefor both CTUs and research funders, since the consistent development of successfulhigh quality proposals requires the investment of adequate time and expertise.Typically, the developmental stage of a new RCT will involve detailed discussionsbetween the chief investigator (from within or external to the CTU) and key CTU staff inthe following activities:

1. Identify the right questions and the optimal trial design2. Conduct systematic reviews (when appropriate)3. Development of sub-studies (when appropriate)4. Coordination of input from different disciplines for different trial components e.g.

quality of life, health economics, translational research (if applicable) andstakeholders, e.g. patients, carers, clinical staff

5. Definition of trial end-points6. Calculation of sample size7. Negotiations and discussions with national and international collaborators (if

applicable)8. Negotiations and discussions with industry collaborators (if applicable)9. Discussions with relevant disease-specific research groups and clinical research

networks (when appropriate)

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10. Establishing study feasibility (e.g. through pilot studies; communication withcollaborative groups and/or the research networks)

11. Consideration of regulatory and governance issues, including identification of aSponsor

12. Development and submission of the grant proposal including costing andscheduling the trial, identifying staff requirements, and sourcing trial supplies(e.g. drug and placebo; assessment tools and equipment)

Oversight of funded trialsThe award of project funding permits the appointment or assignment of specific CTUstaff to work on the ongoing development and subsequent launch and conduct of anRCT. However, CTU core staff, particular senior management staff who are not directlyfunded on the project grant. will continue to be involved in training new staff, overseeingtrial development and delivery, and providing support if an acute need arises in relationto a particular trial (e.g. presentation of new data with implications for the trial question;safety concerns; recruitment problems). Typically, following the award of a grant, staffnot funded directly by the project grant will still be closely involved in the following trial-related activities:

1. Appointment, supervision, and development of project-specific staff: Experienced senior staff (whether in statistics, trial management, IT systems)

are more aware of the critical paths involved in managing projects and betterable to anticipate issues and troubleshoot accordingly. The availability of thisnon-project-specific experience is critical for CTUs in ensuring successfuldelivery across multiple projects by offering project staff high qualitysupervision and mentoring through which they can build on well establishedgood working practices.

2. Oversight of project-specific work in relation to: Finalisation and sign-off of trial protocol and related trial documentation (e.g.

case report forms (CRFs), trial master file and investigator site filedocumentation)

Risk assessment and development of monitoring plan Database development and implementation Regulatory applications (MHRA, ethics, etc), as appropriate Promotion and launch of trial including coordination of investigator meetings Day-to-day management and conduct of trial Pharmacovigilance Preparation of interim and final reports to trial management group (TMG),

TSC, DMC, and funding bodies, organisation of meetings of these groupsand associated secretariat functions (e.g. coordination of recommendationsand actions)

Interim and final analyses and preparation of final study report, includingpublication and dissemination

3. Preparation and negotiation of contracts with collaborators and other stakeholders(e.g. Sponsor, international groups, other collaborating CTUs, industry, clinical sites,pharmacy departments)

4. Ongoing maintenance of key collaborative links (e.g. with clinical research networks,international groups, other CTUs, industry)

5. Negotiation and securing ongoing arrangements for trial supplies

6. Providing contingency support for unexpected circumstances (e.g. sudden long-termsickness of project staff; responding to an urgent safety issue)

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7. Identifying and supporting resources for long-term follow-up beyond the primaryanalysis (often not funded in trial grants)

8. Preparing for GCP inspections carried out by MHRA and other external audits (thisusually requires several weeks/months of preparation whilst still maintaining day-to-day activities for ongoing trials)

9. Ongoing quality control and quality assurance

Management and Strategic Development of the CTUCTUs vary in size but in some cases comprise in excess of 100 staff. Therefore, as wellas the development and delivery of specific projects, time and resources are alsorequired to oversee the general running of the organisation. Consideration must also begiven to the coordination and implementation of the CTU’s strategic development toensure long-term continuity, stability and an environment for career development andencouraging retention of staff and their expertise. This includes:

1. HR issues: Ongoing review of capacity and resource needs and responding to these Consideration of staff development and training needs Negotiation with host institutions regarding recruitment, retention and

promotion of staff, including salaries, job description and adverts etc.

2. Accommodation Negotiating appropriate accommodation with host institution

3. Financial: Management of finances, both general and trial-related Costing new studies Identifying and securing long-term funding Preparation of core funding review documentation and visits

4. Review of CTU infrastructure needs (e.g. IT and QA systems) and responding tothese

5. Building and maintaining long-term strategic relationships with external collaborators

6. Ongoing review of regulatory and governance requirements affecting clinical trials(e.g. EU Directive, GCP Directive, Data Protection Act, Human Tissue Act etc.) andmanaging responses to changes to ensure continued adherence to quality and legalstandards

7. Responding to queries, surveys, and other requests for information from Sponsors,government agencies, research networks, etc.

Methodological DevelopmentIn addition to the delivery of specific clinical trials, CTUs are also critical to the generaldevelopment of the clinical research field in terms of addressing more general academicand practical issues associated with the conduct of clinical trials, and supporting thedevelopment of clinical research more widely through participation in externalcommittees and groups. This may involve staff undertaking the following activitieswhich are independent of project grant funding:

1. Representation and contribution to national and international advisory and reviewcommittees (including grant review committees)

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2. Contribution to membership of Data & Safety Monitoring Committees and TrialSteering Committees for external trials

3. Conducting exploratory analyses and systematic reviews

4. Engaging in methodological research, such as statistical methods, or addressingpractical issues (e.g. remote data entry; consumer involvement).

5. Maintaining awareness and understanding of trial design developments and the useof novel and/or complex designs

6. Maintenance of an in-depth knowledge of the clinical area

7. Maintenance of academic research profile

Training and Professional DevelopmentGiven the stringent regulation of research involving patients, it is imperative that CTUstaff are appropriately trained for the responsibilities they take on and within areasonable timeframe. Core staff within CTUs provide the depth of experience toensure that new staff receive adequate training. Few formal training or professionaldevelopment programmes exists outside of CTUs, particularly in research methods andstatistical expertise, and therefore CTUs provide a n important resource in developingthe clinical research workforce in these areas. Therefore, the following activities, whichare not funded through project grants, are commonly undertake by CTUs:

1. Oversee training and development of new staff

2. Offer career development opportunities for CTU staff

3. Provide mentoring for developing CTUs

4. Provision of training and advice to researchers, trialists etc. external to the CTU

In summary, core funding provides stability, particularly for senior staff, to undertakeand/or oversee the activities outlined above. It also affords key CTU staff theopportunity for professional development, offering clear prospects for careerprogression to high quality specialist staff and increasing the likelihood of long termcommitment from these staff. This stability allows CTUs to build on existing expertiseand experience, and enhances the long term capacity and flexibility of CTUs to developand maintain robust and sophisticated systems (particularly contingency plans) tounderpin RCT activity. This long term stability also has the knock-on effect of providinga unique training environment for developing new expertise. Less experienced CTUstaff have access to the expertise and breadth of experience offered by senior staff,many of whom will engage in formal training programmes for junior clinical and non-clinical CTU staff including supervision of independent research projects leading tohigher degree qualifications. A requirement for CTU registration was that applicantsmust demonstrate resources to provide adequate and stable infrastructure and seniorstaff as well as an ability to ensure continuity of the core disciplines.

Non-staff, non-trial specific costsIn addition to the staff activities described above, a number of substantial but necessarynon-staff costs must also be met by CTUs in order to support the delivery of the clinicaltrials they have responsibility for. These additional costs are non-trial specific andtherefore difficult to recover from project grant funding. These include:

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Systems for clinical data managementMost RCTs are large multicentre studies; a single RCT will usually recruit severalhundred to several thousand patients. The management and storage ofcomplex data on this scale demands robust and formally validated datamanagement systems and these are also critical to supporting trial managementcoordination, such as generation and tracking of data queries. The cost ofestablishing and maintaining such systems is significant, although cost efficiencysavings can be realised once effective systems are in place and the need todevelop bespoke database systems for each new trial is removed.

MHRA GCP Inspection FeesRCTs involving investigational medicinal products (CTIMPs) are subject to theClinical Trial Regulations which transposed the European Clinical Trials Directive(2001/20/EC) into UK law. As a consequence of the Directive, all Sponsors ofCTIMPs are subject to mandatory GCP inspections. CTUs will in most casesbear the brunt of these inspections, even where they are not the Sponsor (sincemost, if not all, of the Sponsor responsibilities are delegated to CTUs).Preparation for the inspections is expensive, as is the fee for the inspectionsitself, being proportional to the size of the unit and the number of CTIMPs theunit is involved with. The minimum cost is somewhere in the region of £15k perinspection.

Attendance at External Training Courses and Scientific ConferencesThe continued development of all CTU staff relies upon opportunities to attendexternal training courses and conferences (e.g. national and internationalscientific conferences; events organised by regulatory authorities). Whilst thecosts of attending some types of external events is covered by project funding,this is usually very limited (e.g. restricted to dissemination of project findings atscientific conferences). Although many external training events and conferencesoffer academic rates, these can still be several hundred pounds per delegate.Without designated core funding, project funding alone provides little scope toensure that both senior and junior CTU staff can benefit and contribute toexternal conferences and training events.

2.3 Benefits of Core Funding

2.3.1 Impact of core funding in NCRI Accredited Units

In 2003 and 2004, nine UK CTUs were accredited by the National Cancer ResearchInstitute (NCRI) (these CTUs were all subsequently awarded UKCRC Registration). Allnine CTUs had demonstrated a strong track record of developing and managing thedelivery of large multicentre cancer RCTs and a review of the core capacity of the NCRIaccredited CTUs was carried out in 2005 [6]. Seven of the nine have received stablecore funding from NCRI partner funders (i.e. Cancer Research UK, MRC, DH) for over10 years, and the two remaining CTUs have recently been awarded core funding fromCancer Research UK.

Following the 2005 capacity review, three of the seven CTUs which had received longterm core funding received enhancement of their Cancer Research UK core funding. All

6 Stead ML & Meade AM (2005) Costs of the National Cancer Clinical Trials Portfolio Part 2: CoreFunding Resource Requirements (for the Development and Management of Phase III Cancer RandomisedControlled Trials)

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three CTUs received an initial increase in core funding in December 2005 in order tosupport the additional demands the CTUs faced in ensuring compliance of their clinicaltrials with the 2004 UK clinical trials regulations. In addition, in February 2006 CancerResearch UK invested further core funding in these three CTUs plus two more recentlyestablished CTUs to strengthen CTU capacity to develop more new, high quality cancerclinical trial proposals and diversify into new tumour sites.

Data have been collected from all of the NCRI accredited CTUs regarding the size oftheir RCT portfolios and their application success rates between 2006 and 2008.

2.3.2 Size of CTU RCT Portfolio

It can take up to 2 years to work up new proposals into funded clinical trials (i.e. frominception to start of recruitment). Therefore, all nine NCRI accredited CTUs were askedto provide details of the size of their RCT portfolio in January 2006 (i.e. following thesecond enhancement of core funding for the three Cancer Research UK funded CTUs)and also January 2008. These data are presented in Table 1.

The data show that in the time following the second increase in their core funding, thethree established Cancer Research UK CTUs collectively increased the number ofnewly funded trials they have in development by 45%, and the number they have opento recruitment by 36%. The two newly core funded CTUs collectively doubled or morethan doubled the number of newly funded trials in development and open to accrualbetween 2006 and 2008. In contrast, the collective data received from the four CTUswhich received no additional core funding indicated a reduction of 43% in the number ofnewly funded trials these CTUs had in development and little change in the number oftrials open to recruitment. This is likely to be due to the need to prioritise and direct coreresources to the management of the existing trials portfolio, particularly with regard toimplementing the UK Clinical Trial Regulations as well as maintaining the increasedlevel of ongoing follow-up in studies closed to recruitment.

These data suggest that core funding levels have a positive correlation and a significantimpact on the capacity of CTUs to develop and secure funding through high qualityapplications for the delivery of new clinical trials.

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Table 2: Summary of change in the RCT portfolio of NCRI Accredited CTUs between2006 and 2008

CR UK funded CTUs receiving increased corefunding (three CTUs)

Jan2006

Jan2008

Difference(% change)

No. of clinical trials in set-up 20 29 +9 (+45%)

No. of clinical trials open to accrual 44 60 +16 (+36%)

No. clinical trials closed with ongoing follow-up 50 54 +4 (+8%)

New CR UK CTUs receiving new core funding (two CTUs)

No. of clinical trials in set-up 4 11 +7 (+175%)

No. of clinical trials open to accrual 5 10 +5 (+100%)


CTUs receiving no additional funding (four CTUs)

No. of clinical trials in set-up 14 8 -6 (-43%)

No. of clinical trials open to accrual 69 70 +1 (+1.5%)


2.3.3 Grant proposal success rate

The CTU capacity review conducted for the NCRI in 2005 indicated that the grantproposal success rates for cancer trials were 60% at both the outline and full applicationstages (i.e. 36% overall) based on information from the Cancer Research UK ClinicalTrials Advisory and Awards Committee (CTAAC). More recent data from CancerResearch UK suggests that the current CTAAC application overall success rate is 36%at the outline stage and 76% for full proposals, giving an overall success rate of 27%.

For the current project, the recent success rate of proposals submitted specifically bythe NCRI accredited CTUs was examined. Data were collected from the nine NCRIaccredited CTUs about their clinical trial applications to CTAAC and the CancerResearch UK Feasibility Study Committee (FSC) between 2006 and 2008. These dataare presented in Table 3.

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Table 3: Summary of Cancer Research UK project grant applications between January2006 and January 2008 by NCRI Accredited CTUs.

CR UK funded CTUs receiving increasedcore funding (three CTUs)

Submitted Successful Successrate

CTAAC outline proposals 18 16 89%

CTAAC full proposals 15 13 87%

Overall CTAAC success 77%

FSC proposals 12 9 75%

New CR UK CTUs receiving new core funding (two CTUs)





CTUs receiving no additional funding (four CTUs)





ALL NCRI accredited CTUs (nine CTUs)





These data indicate that collectively, the NCRI accredited CTUs have a 59% overallsuccess rate of securing funding for phase III clinical trials via the Cancer Research UKCTAAC committee. This is more than double the overall success rate (i.e. 27%) of allapplications made to CTAAC (this figure includes applications submitted by the NCRIaccredited CTUs). A similar scenario can be seen with regard to applications to theFSC where NCRI accredited CTUs have a collective success rate of 79% compared tothe overall success rate of 46%. This suggests that grant applications made incollaboration with experienced CTUs are of a higher standard and therefore have asubstantially higher prospect of success. Cancer Research UK has recognised theimpact of experienced input into new clinical trial proposals and now refers grantapplicants with promising proposals at the outline stage to a CTU working in the diseasearea for support. Following the recent UKCRC CTU Registration Process, this is nowbecoming increasingly common with funders in other disease areas.

The data collected from the NCRI accredited CTUs indicate that those CTUs whichreceived additional core funding in 2006 are developing proportionately more cancerclinical trial proposals (although it should be noted that three out of the four CTUs whichdid not receive additional core funding from Cancer Research UK are not dedicatedcancer research CTUs, but also focus on developing clinical trials in other disease areas

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and applying for project grants from other funders), and have a higher rate of success insecuring clinical trial funding via CTAAC than those NCRI accredited CTUs that did not.

2.3.4 Cost efficiency savings

We attempted to obtain information from Cancer Research UK on whether their corefunded CTUs request less for project grants than other CTUs. However, this informationwas not readily available since project grants are listed by chief investigator rather thanassigned to a CTU. However, anecdotally, Cancer Research UK have indicated thatproject grants awarded to Cancer Research UK funded CTUs are lower in cost.Although there are no real cost savings for Cancer Research UK overall since savingson project grants are diverted to core funds, it could be argued that the high successrate of grant proposals developed by core funded CTUs reflects the high quality of theseproposals, and the expansion of the capacity of these organisations to manage clinicaltrials to the highest standard is more cost efficient overall.

As outlined above, the CTU activities supported by core funding are varied, and thedirect benefits of core funding with regard to these activities are complex and extensiveand therefore difficult to quantify. However, ensuring optimisation of CTU coreresources should result in an increased volume of high quality trial proposals byallowing time to review the most pertinent and relevant research questions throughliterature review and appropriate engagement with clinical collaborators and patients,and also careful consideration of the optimal trial design. Well designed trials stand amuch greater chance of success by securing funding, achieving recruitment on target bysecuring clinician and patient support, timely reporting of results, and hence speedierimpact on NHS practice resulting in patient benefit.

2.4 Current Core Resources in UKCRC Registered CTUs

Core staff are defined as those posts within the CTU which are funded independently ofspecific research grants. Current funding sources for core staff are varied and for thepurpose of this report have been assigned to two categories:

1. formal core funding (i.e. funding awarded specifically to support the CTU’s coreactivities and infrastructure as a whole rather than a particular project orindividual)

2. non-formal core funding (i.e. funding not awarded specifically to support theCTU’s core activities and infrastructure as a whole, but which may be used tosupport individuals carrying out core activities (e.g. individual fellowships ortenures; retained funds/overheads)).

Information about current levels of funding (as of March/April 2008) to provide adequateand stable infrastructure has been collected from the registered CTUs. A total of 21CTUs confirmed that they held formal core funding which is used to support core staffsalaries. (Note that two of the 21 registered CTUs also provide support for four otherregistered CTUs in a formal collaborative arrangement, three of which have noindependent formal core funding and are therefore not counted in Table 4). In addition,one further CTU receives infrastructure funding from the British Heart Foundation (BHF)via its host institution. Whilst this funding is not specifically committed to the CTU, thisCTU has been included in the group of CTUs receiving formal core funding.

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Table 4 summarises the source of formal core funding for these 22 registered CTUs andthe current overall annual funding levels provided by each source and the total annualsalary component of these core grants. The current annual funding for CTUs throughspecific core grants is approximately £15.85m with approximately £12.1m of thisallocated to core staff salaries.

Table 4. Summary of formal core funding provided to registered CTUs

Core Funding Body No. of CTUsFunded

aCurrent Annual CoreGrant Funding £(% Total)

Current Annual SalaryComponent of CoreGrants £ (% Total)

Cancer Research UK 11 7,211,930 (46%) 6,025,425 (50%)

Medical Research Council 2 5,931,931 (37%) 4,047,796 (34%)

British Heart Foundation 1 136,000 (1%) 126,000 (1%)

Dept of Health (England) 5 1,424,160 (9%) 1,094,186 (9%)

WORD (Wales) 2 621,642 (4%) 454,224 (4%)

HSC R&D (N.I.) 1 500,000 (3%) 310,000 (3%)

CSO (Scotland) 1 24,423 (<0.2%) 24,423 (<0.2%)

Total Current Annual Core Grants 15,850,086 12,082,054

aOne CTU receives formal core grant funding from two of the listed funding bodies.

Abbreviations: WORD – Welsh Office of Research & Development; HSC R&D – Health & Social CareR&D; CSO – Chief Scientist Office

Using the data presented in Table 4, an estimate of the approximate formal core fundingassociated with each disease/health research is presented in Table 5. This is splitaccording to funding body.

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Table 5: Estimated current distribution of formal core funded salaries according tofunder and disease/health care need research area.

DiseaseResearchArea

CR UK MRC BHF DH(Engl.)

WORD(Wales)

HPSSR&D(NI)

CSO(Scot)

Total CoreSalary (£)

a

(% OverallCore SalarySpend)

Blood 67,958 63,000 28,888159,846

(1.32)

Cancer 6,025,425 1,599,000 221,642 15,4317,861,497

(65)

Cardiovascular 169,959 63,000 13,250 2,714248,923

(2)CongenitalDisorders

28,88828,888(0.24)

Dementias &Neurodegen.Disease

169,959 28,888 15,431214,278

(1.77)

Diabetes 7,253 98,126 51,667157,046

(1.3)

Ear 0

Eye 51,667 2,71454,381(0.45)

Generic HealthRelevance

82,69582,695(0.68)

Infection 1,225,299 82,695 51,667 2,7141,362,375b

(11.3)Inflammation &Immune System

28,88828,888(0.24)

Injuries &Accidents

0

Medicines forChildren

266,500 292,194 15,431 51,667427,250

(3.54)

Mental Health 237,917 20,503 15,431273,851

(2.27)Metabolic &Endocrine

0

Musculoskeletal 67,958 49,392 15,431 51,667 2,714187,161

(1.55)

Neurology 67,958 28,88896,846

(0.8)Oral &Gastrointestinal

42,138 15,431 2,71460,283

(0.5)

Primary Care 169,959 36,142 82,695 2,714291,510

(2.4)Renal &Urogenital

28,888 2,71431,602(0.26)

Reproductive &Childbirth

182,953 2,714185,667

(1.54)

Respiratory 67,958 15,431 51,667135,055

(1.12)

Skin 67,958 13,25081,208(0.67)

Stroke 42,13842,138(0.35)

Other 67,958 2,71470,672(0.58)

TOTAL 6,025,425 4,047,796 126,000 1,094,186 454,224 310,000 24,423 12,082,054

aThis is based on the formal core funding reported by 22 registered CTUs (see Table 4) and their disease

research interests. In most cases, formal core grant funding (salary component) received by a given CTUhas been divided equally between the disease research interests of that CTU except in cases where it wasclear that a weighted distribution applied.

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Table 6 shows that whilst some disease areas appear to be well resourced in terms ofthe number of registered CTUs, there is little formal core funding in these CTUs toprovide stability and allow further development.

Table 6: Summary of distribution of current registered CTU resources and formal corefunding by disease/health care need research area.

Disease Research AreaNo. of Reg CTUs with

Interest in Disease AreaNo. RCTs in UKCRN

PortfolioAmount of Formal Core

Salary Funding (£)a

Cancer 24 294 7,861,497

Cardiovascular 15 43 248,923

Mental Health 15 42 273,851

Primary Care 16 39 291,510

Medicines for Children 14 34 427,250

Diabetes 13 31 157,046

Stroke 10 30 42,138

Musculoskeletal 16 19 187,161

Reproductive & Childbirth 9 15 185,667

Dementias &Neurodegenerative Disease

9 12 214,278

Respiratory 11 10 135,055

Oral & Gastrointestinal 12 9 60,283

Metabolic & Endocrine 6 8 0

Neurology 10 8 96,846

Skin 7 8 81,208

Infection 9 7 1,362,375b

Renal & Urogenital 3 5 31,602

Injuries and Accidents 4 4 0

Generic Health Relevance 4 3 82,695

Inflammation & ImmuneSystem

5 3 28,888

Blood 6 2 159,846

Eye 3 2 54,381

Congenital Disorders 1 1 28,888

Ear 0 1 0

Other 7 93 70,672

aBased on data presented in Table 5

bNote that a substantial proportion of the infection clinical trials run by registered CTUs recruit patients

overseas. These studies are not included in the UKCRN Clinical Research Portfolio.

Since 18 registered CTUs do not hold formal core grants, these CTUs are not includedin the data presented in Tables 4, 5, and 6 above. The funding to support core staffsalaries in these 18 CTUs is provided via non-formal core funding, the sources of whichare discussed further in the next section.

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2.4.1 Type and number of core staff in Registered CTUs

As part of the UKCRC CTU Registration process, applicants were asked to provide anindication of staff funded independently of specific research grants, whether fromspecific CTU core grants or other sources (e.g. host institution; fellowship awards;retained funds). The types of staff varied between CTUs but descriptions of the typicalcore roles are provided below.

Programme leader (includes CTU directors, deputy/assistant directors,clinicians, lead statisticians, epidemiologists): oversight of development of newtrials, grant applications, on-going trials; development of CTU strategy and externalrepresentation of CTU; conduct of other research activities (e.g. methodologicalresearch); training, staff management and development.

Senior statistician/scientist (includes clinical research fellows, socialscientists, health service researchers, health economists): development of newtrials, grant applications; oversight of on-going trials; supervision/conduct ofexploratory analyses, detailed analyses (beyond the primary analysis), follow-updata analyses, meta-analyses; conduct of other research activities; training, staffmanagement and development.

Junior statistician: assist senior statisticians whilst developing expertise in fullrange of trial development and analysis activities as well as other research activities.

Trial manager (includes senior managers): development of new trials, grantapplications; management and oversight of adherence to quality standards;provision of continued expertise in trial management; management of long-termfollow-up of trials beyond primary analysis; conduct of other research activities;training, staff management and development.

Data manager (includes junior trial manager; trial administrators): assist trialmanager whilst developing expertise in all aspects of trial development andmanagement.

Quality Assurance manager: set-up and implementation of quality managementsystems to ensure adherence to regulatory and governance requirements; performinternal audits as required; training, staff management and development.

Computing staff: management, support, and maintenance of IS/IT systems(hardware, software, trial databases, network services); ensure IS/IT systemcompliance with regulatory requirements; training, staff management anddevelopment.

Business manager: costing new trials; management of financial aspects of thetrials activities; contract negotiation with external parties (e.g. industry funders; trialsites); support for HR matters.

Administrative staff: provision of general office support in the CTU, includingmailshots and routine mail distributions, meeting and event coordination.

CTUs were asked to indicate the WTE contributions of these staff to the developmentand central coordination of clinical trials (as opposed to other research activities such asmeta-analyses, audit, or clinical work) and their source of funding. Table 7 summarisesthe current levels of core funded staff within the 40 registered CTUs and indicates thatthere are currently approximately 516 WTE core staff within the 40 registered CTUs, ofwhich 283.4 (55%) are funded through formal core grants.

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Table 7: Summary of all core funded staff in the 40 registered CTUs and source of funding.

Core Staff WTE by Funding Source

Formal Core Funding Sources Non-formal Core Funding Sources

Core Staff Role TotalWTEbyRole

CR UK MRC BHF DH(Engl.)

WORD(Wales)

HSC R&D(NI)

CSO(Scot)

HEI NHSTrust

TCRNCC

PCRN Retainedfunds/OH

Othera

Clinical Director 13.4 1.2 2 - 1 - 0.5 - 4.13 3.33 - - 1 0.2

Non-Clinical Director 16.3 1.05 - - 2.8 2 - 0.5 9.7 0.2 - - - -

Assistant Director 7.9 3 - - 1.5 0.2 - - 2.8 - - - 0.4 -

Clinician 33.4 1 1 - 0.2 - - - 18.2 8.35 - - 1.4 3.2

Epidemiologist 24.0 - 7 - 1 - - - 9.2 3.9 - - 1.4 1.5

Health Economist 5.5 - - - 1 - 0.7 - 2.45 1 - - 0.33 -

Senior Statistician/Scientist

74.5 13.89 13 1.0 6 1 0.8 - 20.35 11.95 0.2 - 4.65 1.6

Junior Statistician 38.7 16 5 1.0 1.25 2.6 2 - 3.92 5.66 - - 1 0.2

Senior Manager 14.6 8.45 - - 1.4 - - - 1 1.6 - - 1.7 0.4

Trial Manager 77.8 31.7 13.3 - 2 2.6 1 - 8.99 2.5 1.5 1.0 5.7 7.5

Data Manager 30.3 6.5 6.5 - - 2 - 4.8 5 - - 1 4.5

Trial Administrator 24.0 7 2 1.0 - - - 2 3.5 - - 6 2.5

Quality Assurance 36.6 12.7 9 - - 3 - 4 5.25 - - 2.1 0.5

Computing staff 64.1 22.35 20 - 3.75 2.5 1.5 - 2.7 6.5 - - 3.75 1

Business Manager 14.4 7.65 - - 1 1 0.2 - - 2 - - 1.5 1

Administrative staff 41.0 7.42 9 - 3.5 1 1 - 10.2 2 - 0.5 6.4 -

Total WTE byFunder

516.5 142.1 87.8 3.0 29.3 12.9 12.7 0.5 106.9 67.6 1.7 4.8 42.9 24.2

aA list of these funders is provided in Appendix 4

Notes on assumptions made: Where more than one source of funding is indicated for a single post, a 50:50 split has been assumed unless otherwise indicated.Abbreviations: HEI – Higher Education Institution; TCRN CC – Topic-specific Research Network Coordinating Centre; PCRN – Primary Care Research Network;OH – Overheads

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2.4.2 Current cost of core staff

As indicated in Table 7, a significant proportion of core CTU staff are currentlysupported from sources other than formal core grants provided by the funders listed inTable 4. Although there is no formal core salary funding in these CTUs as such, it ispossible to estimate the current salary costs associated with supporting all core stafflisted in Table 7 using salary information collected from the registered CTUs. Table 8presents a summary of the mean salary information collected for the key core staff rolesin registered CTUs.

Table 8. Summary of salary data for core CTU staff roles collated from registered CTUs(excluding on-costs at 20%)

Core Staff Role Mean Lower Limit(£)

Mean Upper Limit(£)

Mean Mid-Range(£)

Director (Clinical) 74,789 103,204 91,091

Director (Non - Clinical) 46,739 58,990 55,138

Asst Director 41,723 55,343 48,533

Clinician 66,765 88,450 79,687

Epidemiologist 40,580 53,583 51,405

Health Economist 34,187 46,352 40,269

Senior Statistician 34,668 46,818 40,743

Junior Statistician 27,733 36,014 31,873

Senior Manager 38,092 46,687 42,389

Trial Manager 27,920 36,893 32,406

Data Manager 22,782 27,924 25,353

Trial Administrator 18,729 23,410 21,069

Quality Assurance 30,995 38,844 34,920

Computing 27,412 38,641 33,026

Business Manager 30,998 39,483 35,241

Secretarial 18,484 23,407 20,946

Using data presented in Tables 7 and 8, a summary of the total estimated core staffsalary costs is presented (by funder) in Table 9 and suggests that the current annualexpenditure on registered CTU core staff salaries is approximately £24m (including on-costs at 20% but excluding overheads). Of this, only half is provided via formal CTUcore funding (see Table 4), whilst the remaining estimated salary costs amongst theregistered CTUs are provided by non-formal core funding sources, such as hostinstitutions (e.g. universities, NHS Trusts) or retained funds and overhead recovery.

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Table 9. Current salary funding of core staff in the 40 registered CTUs (including on-costs at 20% but excluding overhead costs)

Type of Core Funding Funder Core Salary funding (£)

Cancer Research UK 6,025,425

MRC 4,047,796DH (England) 1,094,186

WORD 454,224

HSC R&D (NI) 310,000

BHF 126,000

Formal Core Funding(actual funding in CTUsreceiving formal core grantsas presented in Table 4)

CSO (Scotland) 24,423Total Formal Core Funded Salaries 12,082,054

Higher Education Institute (HEI) 5,867,010

NHS Trust 3,296,996

Retained funds/Overheads 1,585,549

Other 1,121,257

TCRN Coordinating Centre 68,109

Non-Formal Core Funding(estimated core salaryfunding based on datapresented in Tables 7 and 8)

Primary Care Research Network 51,455

Total Non-Formal Core Funded Salaries 11,990,376

Total Formal and Non-formal Core Funded Salaries 24,072,430

2.4.3 Stability of Current Core Staff in Registered CTUs

There are currently 516 core staff within the 40 registered CTUs. However, asdiscussed above, only half of these posts are currently supported by formal CTU corefunding, the remainder being provided through various non-formal core funding sources,for example via host institutions (HEIs and NHS Trusts) or retained funds. RegisteredCTUs were asked to indicate the stability of the funding for their core staff and thisinformation is presented below in Tables 10 and 11.

2.4.3.1 Current core staff funded by formal core funding

Table 10 indicates that of the core staff funded from formal CTU core grants, funding for98% is due to expire by 2010. However, the majority (87%) of these staff posts areconsidered stable as their funding is considered by the relevant CTUs to have a highlikelihood of renewal, although approximately 11% of staff are funded through formalcore grants which are considered uncertain of renewal. A very small proportion (approx.2%) of staff funded from formal core CTUs grants are considered unlikely of renewal orinformation on renewal was not provided by the CTU.

2.4.3.2 Current core staff funded by non-formal core funding

With regard to staff funded via non-formal core funding, the data presented in Table 10indicate that 28% are supported on funding which is not subject to expiry (this includessalaries for HEI and NHS tenured posts), 53% are supported on funding due to expireby 2012, and expiry information for salaries was not provided for 18% of staff supportedby non-formal core funding.

With regard to the 53% of staff that are currently supported on non-formal core fundingdue to expire by 2012, the funding for 65% of these staff (approx. 79 core staff) isconsidered by CTUs to be either uncertain of renewal or unlikely to be renewed.

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Table 10. Stability of core CTU staff in registered CTUs determined by probability of renewal of salary funding. The table below presents abreakdown of current core staff posts based on the expiry of their salary funding and the likelihood of funding renewal. Formal core funded andnon-formal core funded posts are presented separately.

Probability of Renewal of Formal CTU Core Grant Funding(i.e. funded from grant specifically for CTU core activity)

Probability of Renewal of Non-formal Core Grant Funding(i.e. not funded from specific CTU core grants)

Yearfundsend High N/A Uncertain Unlikely N/K Totals (%) High N/A Uncertain Unlikely N/K Totals (%)

2008 94.31 - - 2.0 - 96.3 (34) 6.0 - 17.63 16.2 - 39.8 (17)

2009 50.7 - 1.75 - - 52.5 (19) 11.5 - 17.7 12.6 1.0 42.8 (18)

2010 95.15 - 30.8 - 1.0 127.0 (45) 10.8 - 10.6 - - 21.4 (9)

2011 3.0 - - - - 3.0 (1) 7.1 - 4.5 - - 11.6 (5)

2012 - - - - - 0 6.6 - 1.66 - - 8.3 (4)

2013 0.5 - - - - 0.5 (<1) 0.7 - - - - 0.7 (<1)

No fixedexpiry

3.0 - - - - 3.0 (1) 25.33 33.21 6.8 - - 65.3 (28)

Not given - - - - 1.0 1.0 (<1) 12.47 - 6.18 - 23.95 42.6 (18)

Totals(%)

246.7(87)

032.6(11)

2(1)

2(1)

283.380.5(35)

33.2(14)

65.1(28)

28.8(12)

25.0(11)

232.6

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Table 11 summarises the overall stability of registered CTU core staff. These datasuggest that the funding for approximately 64% of current core staff can be consideredrelatively stable, carrying a high probability of renewal. Approximately 75% of these“secure” core posts are funded from formal core CTU grants.

Approximately 33 (6%) core staff posts are supported on funding which is not subject toexpiry (e.g. where staff are tenured by host institutions) and may therefore be regardedas “secure”. However, whilst these posts may be secure with regard to the member ofstaff concerned, they are often not committed specifically to CTU activity and may nottherefore be secure in terms of providing specific CTU core resources.

It is important to note that the funding for approximately 128 (25%) core staff posts isconsidered either uncertain or unlikely to be renewed and therefore potentially unstable.Approximately 93 of these posts are supported by non-formal core funding which is dueto expire over the next 4 years (i.e. by 2012). Information on the stability of 27 (5%)core posts was not provided.

The data gathered from the registered CTUs therefore suggest that at least 128 of the516 current core posts (at all levels) are not secure but could be stabilisedthrough new or extended formal core grants. The number may be considerablyhigher if those posts where information on stability of funding is lacking, as well as thosewith no fixed expiry (generally more senior staff) which do not necessarily translate toformalised core CTU resources, are also considered as potentially non-secure.

Table 11. Summary of stability of current core staff in registered CTUs

Likelihood offunding renewal

Formal GrantFunding (WTEs)

Non-formal GrantFunding (WTEs)

Total WTEs(% Total)

High 246.7 80.5 327.4 (64)No fixed expiry 0 33.2 33.2 (6)Uncertain 32.6 65.1 97.6 (19)Unlikely 2.0 28.8 30.8 (6)Not given 2.0 25.0 27.0 (5)Totals 283.3 232.6 516a

2.5 Current level of RCT activity

The current level of RCT activity has been estimated using data obtained from theUKCRN Clinical Research Portfolio database and information provided in theregistration application forms of the registered CTUs. As discussed in section 1.2.2, thefocus of the current project is on large late phase RCTs. Therefore, in determining thecurrent level of activity, only late phase RCTs have been included and phase I or IIstudies, feasibility studies, and experimental medicine studies have been excluded. Inaddition, randomised studies with small sample sizes have also been excluded; this hasbeen applied to sample sizes smaller than 40 for multicentre RCTs, and smaller than100 for single centre RCTs (a distinction has been made between single centre andmulticentre RCTs in order to take into account the higher level of complexity associatedwith coordinating multicentre research).

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2.5.1 Current estimated number of RCTs involving registered CTUs

A total of 537 active RCTs were identified from the UKCRN Portfolio database. Thisnumber includes RCTs which are in set-up, open to recruitment, or in follow-up. Ofthese 537 RCTs, 289 were identified as involving a registered CTU. In addition, afurther 159 active RCTs which are not listed on the UKCRN Portfolio database wereidentified from the registration application forms of the registered CTUs (clearly, all ofthese RCTs involve a registered CTU). Of these 159 RCTs, 93 are eligible forautomatic inclusion in the UKCRN Portfolio. It is therefore estimated that the registeredCTUs are currently involved in coordinating a total of 382 active RCTs (i.e. 289 plus 93)which are eligible for inclusion in the UKCRN Clinical Research Portfolio.

It is clear that a number of RCTs which are eligible for inclusion in the UKCRN Portfolioare not yet listed in the Portfolio database (93 such RCTs were identified from the CTUregistration applications). In order to provide a more accurate estimate of the overallnumber of RCTs ongoing in the UK, an assumption must be made that in addition to the93 RCTs involving the registered CTUs, there are a number of further RCTs which areeligible for, but as yet not listed in, the UKCRN Portfolio database, and which are notbeing coordinated amongst the registered CTUs. In order to estimate this number, wehave assumed that the registered CTUs are involved in a similar proportion of listed andunlisted eligible RCTs. Five hundred and thirty seven RCTs are listed in the UKCRNPortfolio database and 289 (54%) of these involved a registered CTU. There were 93non-listed RCTs reported by the registered CTUs. If these constituted 54% of the totaleligible but unlisted RCTs, we can estimate that there are a further 172 RCTs in total.Therefore, the total number of currently active RCTs in the UK can be estimated as 709(537 plus 172), of which the registered CTUs are involved in 382 (54%).

Examining the available data on the 537 RCTs currently in the UKCRN Portfoliodatabase in more detail suggests that the registered CTUs are responsible formanaging a higher proportion of complex RCTs. Currently, 240 of the RCTs listed inthe UKCRN Portfolio database involve an IMP. The registered CTUs are involved in167 (70%) of these CTIMPs. In addition, data from the UKCRN Portfolio indicates thatthe size of the RCTs managed by registered CTUs is approximately double that ofRCTs not managed by registered CTUs (median sample size: 664 compared to 346).

2.5.2 Sources of project grant funding for the current RCT activity

Table 12 provides a breakdown of the key organisations providing specific project grantfunding to support RCTs eligible for inclusion in the UKCRN Portfolio. Information onfunders has been gathered from data held on in the UKCRN Portfolio database orincluded in CTU registration applications. This comprises a total of 630 RCTs: 537already listed on the Portfolio database plus 93 listed in the CTU registrationapplications.

The summary presented in Table 12 focuses on the key funders of RCTs, i.e. thosefunding more than five currently active RCTs. It should be noted that RCTs funded bysome organisations listed below are not automatically eligible for inclusion in theUKCRN Portfolio. These funders are included in Table 12 due their current inclusion inthe UKCRN Portfolio either by virtue of the fact that they are a minority funder of anRCT co-funded with an automatically eligible funder, may have been included in theUKCRN Portfolio as a sole RCT funder prior to the implementation of current eligibilitycriteria, or may have been considered eligible following adoption. Shaded rows in Table12 denote those organisations whose RCTs automatically qualify for inclusion in theUKCRN Portfolio.

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Table 12: Breakdown of the source of project grant funding for 630 RCTs eligible forinclusion in the UKCRN Clinical Research Portfolio identified from the UKCRN Portfoliodatabase and CTU registration application forms. (Note that some RCTs are countedmore than once where multiple funding bodies are involved).

Funder Current No. RCTsFunded (% total RCTs

a)

No. as SoleFunder

No. as JointFunder

Cancer Research UK 152 (24) 106 46

Medical Research Council 104 (17) 78 26

NIHR HTA Programme 78 (12) 75 3

Industry (includes 25 companies) 60b

(10) 34c

26d

Other NIHR (excl. HTA) 50 (8) 40 10

European Organisation For Researchand Treatment Of Cancer (EORTC)

28 (4) 18 10

British Heart Foundation 25 (4) 23 2

Arthritis Research Campaign 19 (3) 18 1

Chief Scientist Office 16 (3) 13 3

Diabetes UK 14 (2) 11 3

Wellcome Trust 12 (2) 11 1

NHS (e.g. Trust R&D) 11 (2) 6 5

The Health Foundation 10 (2) 9 1

Leukaemia Research Fund 8 (1) 6 2

BUPA Foundation 8 (1) 8 0

Stroke Association 7 (1) 3 4

UK University/Research Institute 6 (1) 6 0

All other organisations funding five orfewer RCTs

e 82 (13) 49 33

aCalculated as percentage of 630 RCTs

bNumber of RCTs with at least one industry funding partner

cRCTs funded solely by industry includes RCTs funded by a single or multiple industry partners

dAll RCTs jointly funded by industry are those which also involve a non-industry funding partner

eList of organisations provided in Appendix 6

2.5.3 Current annual level of new RCTs eligible for inclusion in the UKCRNClinical Research Portfolio

Of the 537 RCTs listed in the UKCRN Portfolio, 95 were registered as opening torecruitment in 2007. Of these, 52 (approx. 55%) involved a registered CTU.

In addition, based on information provided in the CTU registration forms there are afurther 20 RCTs which are eligible for (but not yet listed in) the UKCRN Portfolio.Therefore, the total number of RCTs starting in 2007 and involving a registered CTU is72.

It is clear that a number of RCTs which are eligible for inclusion in the UKCRN Portfolioare not yet listed in the Portfolio database. Twenty such RCTs starting in 2007 wereidentified from the CTU registration applications. In order to provide a more accurateestimate of the overall number of RCTs starting in 2007 in the UK, an assumption mustbe made that in addition to these 20 RCTs involving the registered CTUs, a number offurther RCTs also started in 2007 which are eligible for but as yet not listed in theUKCRN Portfolio database, and which are not being coordinated amongst theregistered CTUs. In order to estimate this number, we have assumed that the

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registered CTUs are involved in a similar proportion of listed and unlisted eligible RCTs.Ninety-five RCTs were listed as starting in 2007 and 55% of these involved a registeredCTU. There were 20 non-listed RCTs starting in 2007 reported by the registered CTUs.If these constituted 55% of the total eligible, but unlisted RCTs starting in 2007, we canestimate that there were 36 RCTs in total, and therefore the total number of RCTsstarting in 2007 in the UK can be estimated as 131 (95 plus 36), of which the registeredCTUs are estimated to be involved in 72 (55%).

An estimate of the number of core staff required to develop and deliver this currentannual level of new RCTs will be addressed in the following section.

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3. MODELLING CTU CORE CAPACITY REQUIREMENTS

The National Cancer Research Network (NCRN) undertook a project 3 years ago onbehalf of the NCRI to review the core staff resources needed in NCRI accredited CTUs.Like the current project, the NCRN project focused on modelling the core staff requiredto support the development and delivery of academic-led, late phase RCTs. Thecurrent project has adopted a modified version of the NCRI report model in order toapply it more broadly to core CTU resources required for the design and development ofRCTs across the full spectrum of disease.

3.1 Overview of model developed for 2005 NCRI review

The basis for this model was firstly to identify the key stages of the trial life-cycle and theCTU core staff roles which contribute to each stage. The time required from each ofthese core staff roles in each of the trial stages was then estimated for the developmentand delivery of a one typical cancer RCT.

3.1.1 Description of key stages of trial development and delivery used in model

The model recognises the contribution of six key stages in the trial life-cycle. These aredescribed below.

1. Trial development (pre-award): This stage precedes project funding and thereforerelies heavily on core funded CTU staff to undertake the work involved. In addition,this stage is often protracted to allow for discussions and review of literature inrelation to the research question and consideration of the optimal trial design.

a. Preparation of outline funding application: Following agreement of the researchquestion and the trial design, funding to support the project must then besecured. This generally involves the submission of a formal application to afunding body. Often the first step to securing project funds will involvepresentation of an outline proposal describing the trial objectives and design. Itis important to ensure that outline proposals reflect a realistic plan of the trialdesign and anticipated trial budget. Given the complexity and scale of RCTs,considerable time and effort is spent developing the trial design and consideringthe resources required to deliver it prior to submission of outline proposals.

b. Preparation of full funding application: For proposals which are successful at theoutline stage, applicants will then be invited to submit a more detailed fullproposal. This will include a full appraisal of existing data, a detailed descriptionof the trial design (including power calculations and statistical analysis plan) andtrial procedures (including details of interventions, treatment schedules, and trialmanagement arrangements) as well as funding requirements.

2. Trial development (post-award): Following notification of the award of funding, trialdevelopment can progress with the preparation of the final trial protocol, trialdocumentation, trial data management systems (e.g. case report forms, database,randomisation system), trial supplies, and submission of regulatory applications.Project funding may be released immediately following the award, allowing theappointment of project-funded staff to begin work on this stage with ongoingoversight from core staff. However, in an increasing number of cases, the release offunding may be conditional upon issues such as confirmation of trial sponsor orhaving all required regulatory and governance approvals in place. The work involved

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in arranging sponsorship and preparing regulatory approvals (e.g. ethics; CTA;ARSAC) is substantial, therefore where project funding is withheld, the set-up of thetrial will again rely heavily on the availability of core funded staff.

3. Recruitment: Once set-up, project-funded staff will principally be involved incoordinating the day to day running of the trial, including recruitment of new patients,collection and verification of patient data, monitoring protocol compliance,pharmacovigilance, and addressing any issues and queries from trial sites. Inaddition, this stage also requires preparation of regular reports for funders, ethicscommittees, the trial TSC and DSMC, and ongoing trial publicity and communicationwith participating trial sites. While a large proportion of this work is carried out bygrant-funded staff, core funded staff will be closely involved in overseeing andmaintaining standards for this work.

4. Active follow-up: After completion of recruitment, a period of continued datacollection and verification will usually follow as well as continued communication withthe trial TSC, DSMC, and participating trial sites, and continued reporting to fundersand ethics committees. The coordination of this activity may be managed by project-funded staff but again with continued oversight by core funded staff.

5. Analysis and publication: In accordance with the trial statistical analysis and healtheconomics analysis plans, both project-funded and core funded staff will usually beinvolved in the preparation of the trial database for lock-down prior to primaryanalysis, and the subsequent conduct and presentation of the analysis to fundersand peer reviewed journals. This stage will also involve close liaison with keyexternal trial collaborators including funders. Timescales for publication andresponse to reviewers’ questions often takes longer than the project grant duration,therefore core staff are required to oversee analysis and publication to completion.

6. Long-term follow-up: Secondary trial endpoints in cancer trials usually demandongoing long term follow-up of trial patients beyond the primary analysis hence theinclusion of this final stage. Activity in this stage includes routine requests for follow-up data followed by its verification and database entry, and continued communicationwith trial sites to ensure relevant patient updates are reported to the CTU in a timelyfashion. The level of data management in this stage is considerably less than thatduring the recruitment and active follow-up stages. Nevertheless, the activity placesan ongoing demand on CTU resources for several years. Project funding often doesnot extend through to this stage of the trial life-cycle and consequently, the burden ofmanaging activity in this stage will often fall to core funded CTU staff.

3.1.2 Description of core staff roles used in model

The NCRI model recognised the need for input from both core funded research staff andalso support staff in each stage of trial development and delivery. For the purpose ofthe model, five key research staff roles were identified and four support staff roles.These are described below.

3.1.2.1 Core research staff roles

It should be noted that whilst the five ‘roles’ described below correspond to core stafftitles within CTUs, it is recognised that in some cases other staff may actually carry outthese roles. Examples of the other types of core staff often associated with carrying outthe roles are outlined below.

i. Programme leader: includes CTU directors, assistant directors, clinicians,statisticians, epidemiologists.

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ii. Senior statistician/scientist: in addition to senior statisticians, may also includescientists such as clinical research fellows, social scientists, health serviceresearchers, or health economists.

iii. Junior statistician

iv. Trial Manager: in addition to trial managers, may also include senior managers(e.g. head of trial management; head of disease portfolio)

v. Data Manager

3.1.2.2 Core support staff roles

In addition to the research staff roles described above, core-funded support staff play akey role in underpinning the trial activity by implementing and maintaining generic CTUsystems and processes. Again, whilst the four ‘roles’ described below correspond tocore staff titles within CTUs, it is recognised that in some cases other staff may actuallycarry out these roles.

i. Business manager: includes finance and contract staff

ii. QA staff: includes trial monitors

iii. Computing staff: includes software programmers and IT/IS staff

iv. Administrative staff: includes trial administrators and secretarial staff

3.1.3 Description of model

3.1.3.1 Estimation of core resources required to support trial activity

The first step of the model developed for the NCRI report is presented in Table 13. Thispresents the estimated time required from core research staff at each stage of the triallife-cycle. For the purpose of the model, in estimating the contribution of core supportstaff to each stage of the trial life-cycle it is assumed that the workload of the coresupport staff is directly proportional to the trial-related activity of the core research staff.Therefore, the estimated time contributed by each core support staff role is calculatedas a percentage of the overall time contributed by the core research staff. Thepercentage applied varies according to the core support staff role. For example, in thecase of QA staff, it is estimated that the time contributed at each stage of the trial lifecycle is 10% of the total core research staff time. Therefore, in Table 13, the total coreresearch staff time estimated to be required during the recruitment phase of a singleRCT is 0.4 WTE. The estimated QA staff time required to support the recruitment phaseof single RCT is therefore 0.04 WTE. Respective percentages applied to other supportstaff roles are listed with Table 13.

Table 13 therefore summarises the core research and support staff resources requiredfor the development of one cancer RCT. This model can be factored up to estimate thecore staff requirements for different levels of trial activity, taking into account variablessuch as the anticipated success rate of grant proposals (and therefore the number ofproposals required) to meet the delivery of a given number of trials, and the duration ofthe different stages of trial development and delivery.

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3.1.3.2 Consideration of core resources required for management, and strategic/professional development of the CTU

In order to provide a realistic estimate of core staff resource requirements, the modelmust also take into account other key activities (e.g. management and strategicdevelopment of CTU professional and methodological development – refer to section3.2.1) undertaken by CTU core research staff in addition to trial-related activities. Thisactivity is factored into the model by increasing the time core research staff spend ontrials work by a further 25% (based on approximations provided by the NCRI accreditedCTUs for the amount of time core research staff spend on this activity).

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Table 13. Estimates of the core staff requirements (WTE) for the development and delivery of one academic-led, late phase cancer RCT.

TrialDevelopment(Outline grantapplication)

TrialDevelopment

(Full grantapplication)

TrialDevelopment(Post-grant

award)

DuringRecruitment

ActiveFollow-up

Analysis &Publication

Long-term

follow-up

Programme Leader 0.05 0.1 0.1 0.1 0.05 0.1 0.02Senior Statistician/ Scientist 0.05 0.1 0.1 0.1 0.05 0.1 0.02Junior Statistician 0.025 0.05 0.05 0.05 0.025 0.05 0.01Trial Manager 0.05 0.1 0.5 0.1 0.1 0.1 0.05

Core-fundedResearchstaff

Data Manager 0 0.05 0.1 0.05 0.025 0.05 0.01Total core research staff time 0.175 0.40 0.85 0.40 0.25 0.40 0.11QA staff 0.018 0.040 0.085 0.040 0.025 0.040 0.011Computing staff 0.035 0.080 0.170 0.080 0.050 0.080 0.022Business manager 0.018 0.040 0.085 0.040 0.025 0.040 0.011

Core-fundedSupportstaff Administrative staff 0.026 0.060 0.128 0.060 0.040 0.060 0.017

Notes

0.1 = 1 month over the course of a working year (i.e. 10 month working year)

Levels of core support staff are estimated by calculating a percentage of the total core research staff time. The following percentages wereapplied in the model:

QA staff - 10%

Computing staff – 20%

Business manager – 10%

Administrative staff - 15%

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3.2 Review of NCRI CTU Capacity Model and Adjustments forthe Current Project

The NCRI model was specifically developed to address core CTU resources requiredfor the delivery of cancer RCTs and, as such, incorporates a number of assumptionsbased on the characteristics of a typical cancer trial. The scope of the current projectaddresses RCTs across the full spectrum of disease. A review of the assumptionsmade in the NCRI model was therefore undertaken in consultation with sevenregistered CTUs involved in conducting late phase non-cancer RCTs in order toestablish if, and how, the NCRN model should be adjusted to provide a more genericmodel.

3.2.1 Consideration of assumptions applied

The suitability of the assumptions made with regard to the following variables in theNCRI model were considered by CTUs involved in non-cancer RCTs in order todetermine the relevance to the current project:

1. Grant application success ratesThis variable affects the volume of work required during the trial developmentstages and therefore the amount of time required of core staff. The CTUsconsulted for the current project have experience of applying to a broad range offunding bodies and suggested that an overall grant success rate of 25-30% for latephase clinical trial applications was realistic in relation to their experience of currentgrant applications across a variety of funders.

Consultation with key clinical trial project funders identified a range of applicationsuccess rates. It is therefore difficult in the current project, considering the range offunding bodies involved in supporting RCTs across disease research areas, toselect a standard grant application success rate to apply to the model. As a result,several scenarios are presented which reflect the grant application success rates ofthe largest current clinical trial funders (see section 3.5.2):

Cancer Research UK: overall success rate: 27%Outline proposal success rate: 36%; full proposal success rate: 76%

MRC: overall success rate: 14%Outline proposal success rate: 32%; full proposal success rate: 45%

NIHR HTA Programme (responsive funding stream): overall successrate: 25%Outline proposal success rate: 50%; full proposal success rate: 50%

Although the Cancer Research UK and HTA overall grant success rates are similar,the outline and full proposal success rates in each scenario are distinct anddifferent and therefore impact differently on the resources estimated through themodel.

2. Duration of trial recruitment and follow-up stagesThe duration of trial recruitment and follow-up stages will clearly affect the numberof trials which can be supported at any one time, and therefore the resourcesrequired to support a given number of trials. For the purpose of the NCRI model itwas estimated that for the average cancer RCT the duration of the recruitmentstage is 3 years, the active follow-up stage is 2 years, and the long term follow-up

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stage is 5 years. For the current project, these averages were adjusted as followsbased on consultation with CTUs:

Recruitment stage: whilst half of the CTUs consulted agreed with anaverage recruitment stage duration of 3 years, the others indicated anaverage of 1-2 years. Consequently, for the current project, the averagerecruitment stage duration used was reduced to 2.5 years.

Active follow-up: the active follow-up durations reported by half of theCTUs consulted was 2–3 years and 6-18 months by the other CTUs.Consequently, the average active follow-up duration was maintained at 2years in the current project.

Long term follow-up: consultation with the CTUs indicated that this stageis rare in non-cancer trial (although three CTUs suggested that for some triallong term follow-up was desirable but not feasible due to lack of funding).Consequently, this stage was omitted from the model.

3. Core research staff contributions to each stage of the trial life-cycleTable 13 presents the estimated core research staff contributions to each stage ofthe trial life-cycle. Most of the CTUs consulted for the current project indicated thaton the whole the estimates presented in the NCRI model were applicable to non-cancer trials. However, the trial development stages of non-cancer trials wereconsidered often to be more complex and therefore demanded a higher level ofinput from core CTU staff. Suggested reasons for this included the additional workinvolved in determining appropriate outcome measures which are often not asclearly defined as for cancer trials, and the time taken to set-up and consult withcollaborative groups which are often not well established in many disease researchareas outside of cancer. It was therefore suggested that the time contributed byprogramme leads should be increased during the pre-grant trial development stageby doubling the time contributed to the outline and full grant proposal stages.

With regard to the time contribution of trial manager role, it was suggested that thiswas usually a senior trial manager or an experienced trial manager and thereforethe model should be adjusted to reflect this by using salary for this role appropriateto a more senior member of trial management staff.

With regard to other research staff roles in the NCRI model, the CTUs consultedindicated some variation in the input required during different trial stages. However,these differences were mostly felt to offset each other and for the seniorstatistician/scientist, junior statistician, and data manager roles, no changes weremade to the estimates made in the NCRI model.

Table 14 presents the estimates produced after adjustments to the contributions ofcore research staff to each trial stage for the current project.

4. Core support staff contributions to each phase of the trial life-cycleAs described in section 4.1.3 above, the time contributed by core support staff isestimated as a percentage of the overall research staff time. For the currentproject, the CTUs consulted generally agreed with the percentages used butsuggested that those associated with the more senior support staff roles should beincreased by 2-3%. Therefore, the time contributed by QA managers and businessmanagers was increased from 10% to 12% of research staff time, whilst that forcomputing staff was increased from 20% to 25%. The percentage used to estimateadministrative staff time was maintained at 15% of research staff time.

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The outcome of discussions with CTUs managing non-cancer RCTs suggests that,whilst different research areas might involve varying levels of input from core staff atdifferent stages of the RCT life cycle, the model developed for the NCRI report couldgenerally be applied to other disease areas with some minor adjustments. Theadjustments made to the NCRI model for the current project are presented in Table 14.

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Table 14: Estimates used in the current project of the core staff requirements (WTE) for the development and delivery of one academic-led, latephase RCT.


TrialDevelopment



award)

DuringRecruitment

ActiveFollow-up


Programme Leader 0.1 0.2 0.10 0.10 0.05 0.10Senior Scientist/ Statistician 0.05 0.10 0.10 0.10 0.05 0.10Junior Statistician 0.025 0.05 0.05 0.05 0.025 0.05Senior Trial Manager 0.05 0.10 0.5 0.10 0.10 0.10


Data Manager 0 0.05 0.1 0.05 0.025 0.05Total core research staff time 0.225 0.50 0.85 0.40 0.25 0.40QA staff 0.027 0.060 0.102 0.048 0.030 0.048Computing staff 0.056 0.125 0.212 0.100 0.063 0.100Business manager 0.027 0.060 0.102 0.048 0.030 0.048

Core-fundedSupportstaff Administrative staff 0.033 0.075 0.128 0.060 0.040 0.060

Notes

0.1 = 1 month over the course of a working year (i.e. 10 month working year)

Figures in underlined italics are those which differ after adjustments were made to the NCRI model shown in Table 13.

As before, levels of support staff are estimated by calculating a percentage of the total core research staff time. The following slightlyincreased percentages (except for admin staff) have been applied in this model:

QA staff - 12%




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3.3 Application of adjusted model to current level of RCTactivity in registered CTUs

As discussed in Section 2.5.3, it is estimated that in 2007, 131 new RCTs (which wereeligible for inclusion in the UKCRN Portfolio) started in the UK, and that the registeredCTUs were involved in the coordination of approximately 72 (55%) of these RCTs. Ifthe number of new RCTs starting each year remains at the 2007 level, the overall levelof RCT activity would eventually reach a steady state in which the number of RCTs ineach stage of the RCT life cycle was more or less constant. The resources required tosupport this steady state of activity based on 72 new RCTs per year can be estimatedusing the model presented in Table 14 and this is presented in Table 15. Note that inthe example, a grant application success rate of 50% at both outline and full proposalstages is assumed. Applying this assumption, a steady state of 72 newly fundedRCTs starting each year would require the registered CTUs to be involved in thedevelopment of:

288 outline grant applications (approx. 7 per CTU) per year

144 full grant applications (approx. 3.5 per CTU) per year

Post-grant development of 72 successfully funded RCTs (approx. 2 perCTU) per year

Assuming the average RCT recruitment duration is 2.5 years, and active follow-upduration is 2 years (as discussed in Section 3.2), at steady state of 72 newly fundedRCTs starting each year, registered CTUs would also be involved in managing thefollowing each year:

180 RCTs open to recruitment (approx. 4.5 per CTU)

144 RCTs in active follow-up (approx. 3.5 per CTU)

72 RCTs undergoing analysis and publication (approx. 2 per CTU)

As shown in Table 15, it is estimated that the estimated overall number of core staffrequired to support a steady state of 72 new RCTs per year and support key indirecttrial activities within CTUs to 633 (419 core research staff plus 214 core support staff).

Applying different grant success rates to the model will generate different estimates ofthe number of core staff required to support a given level of RCT activity. Forexample, by applying the Cancer Research UK (CTAAC) grant success rates (36%and 76% for outline and full application, respectively), the estimated number of coreCTU staff needed to support a steady level of activity involving 72 new RCTs per yearis 576; whilst applying the MRC grant success rates (32% and 45% for outline and fullapplication, respectively) the estimated number of core CTU staff needed is 738.

In summary, these various grant application success rates produce a range ofestimates which suggest that the number of core staff required to optimally support asteady level of activity of 72 new RCTs per year is between 576 and 738. Bearing inmind that the actual number of core staff currently in post within the registered CTUs is516, these calculations suggest that between 60 and 222 additional core staff areneeded to optimally support and maintain the quality of the current level ofactivity. This shortfall is mainly in the senior/clinical staff categories within the modeland it is likely that this is currently being met by project funded CTU staff.

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Table 15: Estimate of CTU core resources (WTE) required to support the current level of activity at steady state. This is based on the registeredCTUs managing 72 new RCTs per year.


288 proposals

TrialDevelopment


144 proposals


award)

72 new RCTs

DuringRecruitment

180 RCTs

ActiveFollow-up

144 RCTs


72 RCTs

TOTALCore Staff

WTEs

Programme Leader 28.8 28.8 7.2 18 7.2 7.2 97.2Senior Scientist/ Statistician 14.4 14.4 7.2 18 7.2 7.2 68.4Junior Statistician 7.20 7.2 3.6 9 3.6 3.6 34.2Senior Trial Manager 14.4 14.4 36 18 14.4 7.2 104.4


Data Manager 0 7.2 7.2 9 3.6 3.6 30.6Total core research staff time 64.8 72 61.2 72 36 28.8 334.80QA staff 7.78 8.64 7.34 8.64 4.32 3.46 40.18Computing staff 16.2 18 15.3 18 9 7.2 83.7Business manager 7.78 8.64 7.34 8.64 4.32 3.46 40.18

Core-fundedSupportstaff Administrative staff 9.72 10.8 9.18 10.8 5.4 4.32 50.22

TOTAL Core Research and Support Staff WTEs 106.27 118.08 100.37 118.1 59.04 47.23 549.07

Notes

Levels of support staff are estimated by calculating a percentage of the total core research staff time. The following percentages have beenapplied in this model:

QA staff - 12%




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4 ESTIMATING ADDITIONAL FUTURE CTU CORERESOURCE REQUIREMENTS

4.1 Anticipated change in number of RCTs in UKCRN ClinicalResearch Portfolio

In section 2.5.2, a breakdown of the key RCT project grant funders was presented andthose whose projects automatically qualify for inclusion in the UKCRN Clinical ResearchPortfolio are highlighted in Table 12. In order to obtain an indication of the future levelof RCT activity associated with the UKCRN Portfolio, these funders were asked toindicate any anticipated change in the level of clinical trial activity they fund over thenext 3 years. Table 16 summarises the responses from these funders showing theforecast change in clinical trials funded compared to current levels.

Table 16: Summary of the anticipated change in number of clinical trials funded by keyUKCRN Portfolio funders over the next 3 years

Forecast Cumulative Change in Number of RCTs inRelation to 2007

Funder

2009 2010 2011

NIHR HTA Programme +20 +38 +48

MRC-NIHR Efficacy &Mechanism EvaluationProgramme

+10 +10 +10

Other NIHR (excl. HTA) 0 +10 +10

Arthritis Research Campaign +1 +3 +4

Wellcome Trust +1 +2 +3

Chief Scientist Office +1 +2 +2

Cancer Research UK 0 0 0

Industry (10 companies) 0 0 0

Diabetes UK 0 0 0

British Heart Foundation 0 0 0

The Health Foundation 0 0 0

Stroke Association 0 0 0

BUPA Foundation 0 0 0

Medical Research Council -10 -10 -10

Cumulative Change in No. ofNew RCTs per Year

+23 +55 +67

Therefore, in addition to the current estimated level of 131 new RCTs starting in 2007 inthe UKCRN Portfolio, an additional 23 RCTs are expected to be funded in 2009, anadditional 55 in 2010, and an additional 67 in 2011.

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4.2 Anticipated change in the proportion of UKCRN ClinicalResearch Portfolio RCTs managed by the Registered CTUs

It is estimated that the registered CTUs are currently involved in coordinatingapproximately 55% of UKCRN Portfolio RCT activity. Table 17 presents the number offuture RCTs the registered CTUs would coordinate if their involvement remains at 55%of RCTs in the UKCRN Portfolio, taking into account the increase in the overall numberof new RCTs starting in the next 3 years (as presented in Table 16). However, it is alsoexpected that the proportion of RCTs which the registered CTUs will be involved willincrease over the next 3 years in response to conditions set by funders for investigatorsto work more closely with CTUs on the development and management of new RCTs.Therefore, Table 17 also presents several additional scenarios where the registeredCTUs are involved in coordinating a higher proportion of the UKCRN Portfolio RCTs.The shaded rows in Table 17 present what are considered to be the most likely andfeasible scenarios over the next 3 years.

Table 17: Anticipated number of UKCRN Portfolio RCTs starting in next 3 years andnumber coordinated by registered CTUs according to different scenarios where theproportion of UKCRN Portfolio RCTs involving the registered CTUs is varied.

YearEstimated No. New

Portfolio RCTsProportion New RCTs

Managed by Registered CTUsNo. New RCTs Managed

by Registered CTUs2007 131 55% 72

55% 85

60% 92

65% 1002009

154(131 + 23 new

RCTs)70% 108

55% 102

60% 112

65% 1212010

186(131 + 55 new

RCTs)70% 130

55% 109

60% 119

65% 1292011

198(131 + 67 new

RCTs)70% 139

4.3 Estimated CTU Core Resources Required to SupportAdditional Future RCT Activity

Based on the anticipated increase in RCTs starting over the next 3 years (Table 16), themodel can be used to estimate the optimum number of additional registered CTU corestaff required to support the anticipated increases in the number of new RCTs which theregistered CTUs are likely to be involved in launching over the next 3 years.

Based on the assumptions made regarding the average duration of RCTs (detailed inSection 3.2), it is estimated that if by 2011, the number of new RCTs starting per yearreaches 198 (i.e. 67 additional to the current number of 131 per year), and remains

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constant at this level in subsequent years, then it is anticipated that a steady state ofRCT activity will be reached by 2017/2018.

Table 18 shows the estimated number of additional RCTs which the Registered CTUsmay be expected to be involved in over the next few years following on from the likelyscenarios highlighted (by shading) in Table 17 (i.e. that they will be involved in 55% ofnew RCTs in the UKCRN Portfolio in 2009, increasing to 60% by 2010, and to 65% by2011). The data demonstrate how the anticipated increases in the number of RCTsstarting each year in the registered CTUs will impact on the number of additional RCTsin the accrual, active follow-up, and analysis stages which the registered CTUs will beresponsible for managing in subsequent years. These figures are additional to thenumber of RCTs which the registered CTUs would be expected to be involved in if boththe number of new RCTs starting each year, and the proportion managed by registeredCTUs, do not change.

Table 18 also provides an indication of the year on year increases in additional corestaff required to support the rise in activity, along with estimated costs. The numbersrequired reach a plateau as the number of trials in each stage of development ordelivery reach a steady state. Once again, a variety of grant success rates have beenused which impact on the number of proposals developed and account for the range ofcore staff numbers and costs shown against each of the yearly scenarios in Table 18.Using the model. it is estimated that between 453 and 501 additional core staff will beneeded by 2017/2018 to provide optimum support, assuming that the number ofadditional RCTs which the registered CTUs manage remains steady at 57 per year after2011.

However, assuming that core staff levels are steadily increased at a rate similar to thatindicated in Table 18, it is anticipated that some efficiency savings can be made. It issuggested that efficiency savings of around 7% may initially be made, rising to 13% asnew staff are trained and develop the experience to streamline processes and systemswithin the CTUs for trial development, management, and analysis. Taking into accountthese potential efficiency savings, therefore it is estimated that between 394 and 436additional core CTU staff are needed by 2017/2018 to provide optimum support tothe additional RCTs which registered CTUs are expected to be involved in startingfrom 2009. The range in the estimated additional core resources required reflects thedifferent grant applications success rates used in the model. It is anticipated that withoptimal core resources in place, grant success rates would move towards the highergrant success rate, and therefore the number of additional core staff required by 2017would be closer to the lower figure (i.e. 394).

Finally, it is important to note that this estimate relates specifically to the resourcesneeded to support the anticipated additional new RCTs each year. It does not take intoaccount the lack of stability of a significant proportion of current core staff posts inregistered CTUs (as discussed in section 2.4), nor the estimated shortfall in core postsrequired to support the existing level of RCT activity (as discussed in section 3.3).

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Table 18: Estimated additional core resource requirements per year to support additional RCT activity (i.e. over current level of activity) andestimated costs (including 20% on-costs, but excluding overheads). Shaded cells denote those scenarios which are expected to be less likely asinvestment in core resources becomes effective, increasing expertise and experience in trial development and therefore grant success.

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018Proportion of new RCTs managed by Reg’d CTUs 55% 60% 65% 65% 65% 65% 65% 65% 65% 65%

In start-up +13 +40 +57 +57 +57 +57 +57 +57 +57 +57

In accrual 0 +13 +53 +104 +134 +143 +143 +143 +143 +143

In active follow-up 0 0 0 +7 +33 +75 +106 +114 +114 +114

In analysis 0 0 0 0 0 +7 +27 +49 +57 +57

Estimated cumulativenumber of additionalRCTs:

Total of all ongoing +13 +53 +110 +167 +224 +282 +332 +363 +371 +371

With 32%/45% grantsuccess rate

+87 +276 +420 +461 +497 +528 +557 +578 +584 +584


+68 +218 +363 +378 +413 +444 +474 +495 +501 +501

Estimated cumulativenumber of additionalcore staff required(WTE):

aWith 60%/60% grantsuccess rate

+57 +184 +289 +330 +366 +397 +426 +447 +453 +453

7% efficiency saving applied 10% efficiency saving applied 13% efficiency saving applied


+87 +257 +391 +429 +447 +475 +501 +503 +508 +508


+68 +203 +338 +352 +372 +400 +427 +431 +436 +436

Estimated cumulativenumber of additionalcore staff required (WTE)INCLUDING EFFICIENCYSAVING:

a With 60%/60% grantsuccess rate

+57 +171 +269 +307 +329 +357 +383 +389 +394 +394


4.6m 13.5m 20.4m 22.2m 23.2m 24.4m 25.7m 25.8m 26.2m 26.2m


3.5m 10.5m 16.1m 18.0m 19.1m 20.3m 21.6m 21.8m 22.1m 22.1m

Estimated cumulativecost of additional corestaff required (£)INCLUDING EFFICIENCYSAVING plus 20% on-costs:

a With 60%/60% grantsuccess rate

2.9m 8.8m 13.7m 15.6m 16.7m 18.0m 19.3m 19.6m 19.8m 19.8m

aBaseline used to calculate additional staff is the number of staff estimated to be required to support a steady state of 72 new RCTs starting per year (i.e. 738 for 32%/45% grant

success rate; 633 for 50%/50% grant success rate; 576 for 60%/60% grant success rate. Refer to Section 3.2).

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5 DISCUSSION

The unprecedented levels of investment which have gone into developing andstrengthening clinical research infrastructure in the UK over recent years has beenaccompanied by an expansion in the portfolio of clinical research projects beingundertaken reflecting significant increases in project funding opportunities. Clinical trialsunits (CTUs) play a key role in providing the dedicated expertise and support necessaryfor the design, development, management, analysis and publication of high qualityclinical research. Large-scale RCTs in particular, are pivotal in providing reliableanswers about the clinical benefits and risks and the cost effectiveness of newtherapeutic interventions. RCTs often involve hundreds or thousands of patients,making their design, coordination, monitoring, and analysis a complex process,particularly in the case of CTIMPs where stringent regulations apply. CTUs provide thisexpertise through well established multidisciplinary teams, and funders of clinicalresearch are increasingly looking for evidence that investigators have involved CTUexpertise in the development of clinical research proposals, and intend to continueworking with the CTU on the delivery of the project as an indication of quality assurance.The demand for expertise within CTUs is therefore expected to increase as theinvestment in other aspects of the UK clinical research environment takes effect. Inorder to ensure that CTUs can keep up with this demand, this project reviewed existingCTU capacity and assessed the need for further development and strengthening of thiskey resource.

5.1 Review of Current and Future Registered CTU CapacityRequirements

5.1.1 Current Capacity to support the UKCRN Clinical Research Portfolio

With regard to the availability of registered CTUs in each disease/health research area,a summary of the number and geographical distribution of registered CTUs acrossdisease/health research interests was presented in Table 1 and Appendix 3,respectively. There appear to no obvious geographical gaps with regard to thedistribution of disease/health research interests of registered CTUs. Whilst it isrecognised that the number of CTUs in some disease areas is small (e.g. eye;congenital disorders; injuries and accidents) and therefore geographical coverage islimited, the number of CTUs in these cases appears to be consistent with the size of thenational portfolio for those areas as shown in Table 6. Since most of the registeredCTUs expressed a willingness to work remotely with investigators, the more limitedgeographical distribution of CTUs catering for these smaller disease portfolios shouldnot present major difficulties.

There are currently 516 core staff within the 40 registered CTUs which includesresearch staff such as CTU directors or programme leaders, statisticians, trialmanagement staff, as well as support staff such as those involved in quality assurance,database and information systems, and financial/contracting roles. However, only 22registered CTUs currently receive any formal core funding, and only 55% of core staffposts overall within the 40 registered CTUs are supported by formal core grant funding.The data gathered from the registered CTUs therefore suggest that at least 128 of the516 current core posts are not secure due to the renewal of funding being unlikely oruncertain, and therefore compromise the ability of CTUs to plan and develop long termstrategies and maintain core systems and processes (e.g. quality assurance;mentoring).

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The majority of these ‘non-secure’ posts are currently funded by non-formal corefunding which is due to expire within the next 4 years and affects core CTU staff at alllevels. This highlights a key issue within CTUs since the lack of stable formal corefunding creates problems with regard to retaining vital expertise and experience, whichin turn has significant implications for CTUs in terms of their ability to develop andsupport a strong portfolio of clinical research studies. Evidence gathered from theNCRI-accredited CTUs supports this where CTUs receiving additional investment incore funding from Cancer Research UK reported a greater increase in the size of theircancer RCT portfolio compared to those CTUs which did not receive further corefunding, and also have a higher overall rate of success in securing funding for cancertrials. The existence of a stable core workforce within CTUs ensures that CTUs havethe necessary infrastructure to oversee the development and management of a portfolioof RCT, as well as ensuring other areas of activity which are not typically covered byclinical trials project grants but are essential to the ongoing development of the CTU arenot neglected (e.g. maintenance of quality assurance, general data management, andbusiness/financial systems; management and strategic development of the CTU;training, supervision, and professional development of CTU staff).

5.1.2 Future capacity required to support the UKCRN Clinical Research Portfolio

The contribution of the 40 registered CTUs to current RCT activity was presented inSection 2.5. Based on data gathered for 2007, it is estimated that registered CTUs areinvolved in managing approximately 55% of RCTs in the UKCRN Clinical ResearchPortfolio. This currently translates to the registered CTUs launching around 72 newRCTs per year. Assuming the current level of new RCTs continues (i.e. the registeredCTUs continue to launch 72 new RCTs per year), it is estimated that between 576 and738 core CTU staff would be required to optimally support this level of ongoing RCTactivity. Therefore, regardless of whether the anticipated increases in the number ofRCTs occurs over the next few years, between 60 and 222 extra core staff than arecurrently in place in the registered CTUs are required to continue to support and sustainthe current level of RCTs activity in the UKCRN Portfolio. This shortfall mainly concernsposts in the senior/clinical staff categories.

Notwithstanding this estimated shortfall in the number of care staff required to sustainthe current level of activity, it is anticipated that the number of RCTs which theregistered CTUs are involved in launching and managing will increase over the next 3years. This reflects an anticipated expansion in the number of RCTs funded, along withthe growing tendency for funders to seek confirmation from investigators that they haveobtained expert input into the design of new trials and have collaborative arrangementsin place to work with CTUs on their management. This is particularly true in the case ofmore complex RCTs, such as large scale studies or CTIMPs. Therefore, by 2011, it isestimated that the registered CTUs will be involved in launching around 65% of newRCTs in the UKCRN Portfolio, which itself will have expanded. It is estimated that thiswill equate to the registered CTUs being involved in an extra 57 new RCTs per year by2011 (i.e. 129 per year), resulting in an extra 371 ongoing RCTs (i.e. RCTs in start-up,accrual, follow-up, or analysis) over the current level of activity by 2017, assuming thelevel of new RCTs starting each year remains steady. In order for the registered CTUsto provide the necessary expertise required to support and deliver this additional futureactivity, it is estimated that between 394 to 436 additional core CTU staff will be neededby 2017.

It is important to note that these additional 394 to 436 core staff posts relate to thesupport required to develop and deliver the anticipated future increase in activity. Thesenumbers do not take into account the shortfall of 60 to 222 core staff which relates to

44

the core staff required to optimally sustain and support the current level of activity. Inaddition, it is likely that, unless the issue of the lack of stability in current core fundedposts is addressed, any additional investment in core CTU staff will be utilised in the firstinstance to stabilise existing posts funded by non-CTU specific funding (e.g. retainedfunds/overhead recovery) or project funding. This will have the effect of reducing anyimpact of new funding released to create the new posts needed to support theexpanding RCT portfolio.

5.2 Considerations for the Expansion of Core CTU Resources

In order for registered CTUs to provide optimal support for 65% of RCTs in the UKCRNPortfolio, it recommended that the following additional posts are created between 2009and 2017:

1. an increase of between 394 to 436 additional core CTU staff by 2017 to supportadditional RCTs which registered CTUs may be expected to manage in future

2. an increase of between 60 and 222 core CTU staff to effectively support thecurrent level of RCT activity in the registered CTUs

3. stabilisation of at least 128 existing core CTU staff posts which are not fundedvia stable sources to ensure current activity and future CTU support for RCTs inthe UKCRN Portfolio is not undermined.

Whether this level of expansion in CTU core capacity discussed above can be realised,and how, will be influenced or limited by a number of factors. These include thefollowing considerations:

1. identification of research areas requiring expansion

2. capacity to accommodate the expansion of core staff numbers

3. availability of staff with appropriate expertise

4. mechanisms for increasing funding

Each of these issues is discussed further below.

5.2.1 Identification of research areas requiring expansion

With regard to the expansion in the number of CTU staff, it is difficult to comment onwhether this expansion in core CTU resources should be focused within particulardisease/health research areas as the anticipated increase in RCT funding from the mainfunders over the next 3 years is not associated with a specific disease. The possibleexception to this is the musculoskeletal research portfolio where a modest increase isexpected.

A further consideration is that, whilst some disease areas appear to be well resourced interms of the number of CTUs focusing on these areas of research, there is little or noformal core funding in some of the CTUs within some research areas (Table 6). As aconsequence, the stability of core staff posts in these CTUs is likely to be low whichcarries significant implications in terms of their long term capacity and development.

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5.2.2 Capacity to expand current CTU Core Resources

The potential options for delivering the required increase in CTU core resourcerequirements include:

1. Expansion within registered CTUsFocusing the increase in core CTU staff in the UK within registered CTUs presents anumber of advantages. These include:

existing infrastructure and systems are already in place (e.g. appropriateaccommodation for staff and data storage; QA systems; data and informationmanagement systems)

experienced senior staff in place to train and develop new expertise

track record of developing and managing RCTs

well established collaborative relationships with other research groups (e.g.health economics; research networks)

Information was requested from the 40 registered CTUs regarding their potentialcapacity to expand their staff numbers in their current accommodation and this issummarised in Table 19.

Table 19: Potential capacity of the registered CTUs to expand staff numbers withincurrent accommodation.

Capacity to expand No. Registered CTUs Potential additional staff0 3 -1-3 staff 4 4 – 124-6 staff 8 32 – 487-9 staff 10 70 – 9010+ staff 10 100 - ?Yes but not specified 3 N/KNo response 2 -TOTAL 40 206 – 250+

The data collected suggest that the registered CTUs have considerable capacity toexpand their staff numbers. Collectively, it is estimated that the registered CTUscould accommodate at least 206 additional new staff (this does not take into accountfurther potential expansion which might be accommodated through acquisition ofadditional office space). It is also worth noting that a further round of UKCRC CTURegistration is planned for 2009 and it is anticipated that the number of registeredCTUs will increase.

2. Expansion within existing non-registered CTUsEffective expansion of core staff in non-registered CTUs is, in most cases, likely torequire greater investment than in registered CTUs due to the need to ensure thatCTU infrastructure systems are also adequate to meet the requirements ofmanaging a portfolio of large scale RCTs. However, investment in established non-registered CTUs provides the advantage of allowing these CTUs to work towards fullUKCRC registration status. Any investment in core infrastructure of non-registeredCTUs could carry the condition that UKCRC registration must be achieved within a

46

specified timeframe, and that they should work closely in a mentoring arrangementwith a registered CTU.

3. Creation of new CTUsInvestment in existing CTUs (whether registered or not) presents a more costeffective option than creating new CTUs. New accommodation must be identifiedfor CTUs, as well as procurement of database systems and equipment. These costswould be over and above those considered in the current project. Moreover, anentire CTU team would have to be established and time taken to establish theexpertise for the full functions required of the CTU. Establishing new CTUs mustalso take into account the level of engagement and support from potential hostinstitutions. Any investment in new CTUs could again carry the condition thatUKCRC registration must be achieved within a specified timeframe, and that theyshould work closely in a mentoring arrangement with a registered CTU.

4. Utilise expertise within other organisationsThere may also be scope to utilise expertise within other organisations, for exampleNIHR Research Design Services (RDS), NIHR Collaborations for Leadership inApplied Health Research and Care (CLAHRC), and MRC Hubs for TrialsMethodology Research (HTMR). However, whilst the expertise of CTUs covers thefull spectrum of clinical trials development and delivery (covering trial design,coordination, data management and analysis and publication), the remit of the RDSis specific, focusing on the development and design of high quality researchproposals, whilst CLAHRCs focus on implementation research and HTMRs have aspecific remit of methodological research.

5.2.3 Availability of CTU expertise to permit expansion

The limited availability of expertise in clinical trial design, conduct and analysisnationally has already caused difficulties in recruitment to registered CTUs. Creatingnew CTUs is likely to exacerbate this by distributing the existing expertise more thinlyand could compromise the function of established CTUs by depleting them of key seniorstaff, whilst failing to provide a critical mass of expert and experienced staff to allow newCTUs to establish themselves within a realistic timeframe. It is therefore essential thatexpansion of CTU core resources incorporates a strategy to facilitate the training anddevelopment of existing and new CTU personnel in order to bridge the expertise gap.

Investment in the expansion of existing CTUs would facilitate the development of newexpertise as these CTUs will be well placed to develop new staff and overseeprogression of existing staff into more senior roles. In the medium to longer term,having ensured adequate expansion of expertise in established CTUs, the distribution ofexpertise to less developed or new CTUs will be more feasible and less likely to have anegative impact on the capacity of established CTUs. However, in order to fully addressthe shortage of expertise, a comprehensive workforce development strategy, similar tothose developed under the auspices of UKCRC for other research professionals suchas doctors and dentists and research nurses, is required for CTU staff at all levels, fromsenior clinicians, epidemiologists, statisticians and trial management staff to qualityassurance managers and information systems staff. Initiatives may include theintroduction of fellowship programmes (further to those recently announced as part ofthe NIHR Research Methods Programme) and provision of higher degree trainingopportunities (e.g. MSc in trial management or clinical research), ensuring that suchtraining is flexible and affordable in order to maximise access by CTU staff.

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In summary, initial investment in established CTUs is likely to offer the most costeffective and timely approach to expanding CTU capacity in the UK. However, in orderto address the shortage of expertise, a comprehensive workforce development strategy,similar to those developed under the auspices of UKCRC for other researchprofessionals such as doctors and dentists and research nurses, is required for CTUstaff at all levels, from senior clinicians, epidemiologists, statisticians and trialmanagement staff to quality assurance managers and information systems staff.

5.2.4 Mechanisms for increasing core CTU resources and implications forfunders of UKCRN Portfolio RCTs

Whilst the anticipated expansion of RCTs in UKCRN Portfolio over the next few yearsreflects increases in the number of RCTs supported by some key funders, it is importantto note that existing CTU core capacity is considered to be sub-optimal, with a shortfallin the number of core CTU staff needed to efficiently support current RCT activity andthat at least 25% of current core staff posts are considered either uncertain or unlikely tobe renewed when their funding expires over the next 4 years.

Delivery of the necessary investment in core CTU resources is likely to be approachedby funders in different ways. This may be influenced by funders’ existing budgetallocations and the balance between the funding available to CTUs via core grantsversus project grants. For example, some funders may be in a position to increase theirlevels of investment in CTU core infrastructure via formal CTU core grants, with theexpectation that savings can be made against subsequent project grant fundingrequested by CTUs due to efficiency savings created by optimisation of core resourcesand systems, as well as CTUs moving away from the piecemeal approach of recoveringa proportion of their core costs via project grants. As discussed in section 2.3.4, CancerResearch UK have invested heavily in recent years in CTU core infrastructure andanecdotal evidence suggests that project grants awarded to Cancer Research UK CTUsis lower.

If funders do not have the scope to commit significant amounts of funding to formal coreinfrastructure grants, they may be able to contribute to the expansion of CTU coreresources by increasing project grant funding to include an element which is specific tocore activity. As previously discussed, this approach to funding core staff does notgenerally provide the level of security, sustainability, and flexibility which is critical tosustaining CTU stability due the piecemeal nature of this type of funding (full timesalaries for core staff can rarely be justified within single project grants). However,funders taking this approach may in future consider making a distinction in project grantapplications between funding requested to support project-specific activities andadditional non-project specific funding requested to support core activities in order toensure investment in core capacity via project grants can be readily identified.

The National Institute for Heath Research (NIHR), through the HTA programme, hasrecently committed additional funding to strengthen the capacity of CTUs in Englandthrough a system of rolling support contracts whereby successful CTUs receive ‘primingfunding’ prior to project grant applications. A proportion of this funding (80%) is thenoffset against subsequent successful NIHR project grants awarded to the CTU. A totalof £3.5m was awarded across 17 registered CTUs following the first call for this initiativein June 2008; it is anticipated that, collectively, the CTUs potentially retainapproximately £700k of this per annum for core support.

Whilst this arrangement acknowledges the need to support and retain the core CTUexpertise associated with grant development, core CTU activities are broad, coveringnot just new grant development, but the oversight of ongoing research, strategic

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development of the CTU, and professional and methodological development (asdescribed in section 3.2). Therefore, whilst it is of considerable benefit to CTUs inEngland to have some funding to cover clinical trial development prior to project funding,this funding alone is not sufficient for a core CTU team to effectively manage a portfolioof clinical trials and sustain the ongoing development of the CTU and its staff, all ofwhich ultimately contributes to the quality and efficiency of project delivery. It shouldalso be noted that this funding initiative does not extend to the eight registered CTUs inScotland, Wales, and Northern Ireland.

Finally, CTU host institutions stand to gain considerable income via overheads/FEC onboth the core grants and project grants to their CTUs. Amongst the 40 registered CTUs,32 are hosted by Higher Educations Institutions (HEIs). Therefore, HEIs as a groupneed to be fully engaged in discussions regarding the key role CTUs play in leading andsupporting clinical research in the UK so that they recognise the potential benefit ofstabilising CTUs not least because of the additional project funding that is likely to beobtained over the longer term. By working with CTUs and funders which provideoverhead costs/FEC, it is hoped that business models could be developed in HEIs toensure that monies obtained through overheads/FEC on CTU grants are directedtowards the development and support of CTU activity within their organisations.

5.3 Concluding remarks

This review has considered current capacity and predicted requirements in the UK tosupport the development and delivery of academic-led, late phase RCTs in the UKCRNClinical Research Portfolio. It has focused specifically on the core resources in the 40UKCRC Registered CTUs, and their capacity to provide the expertise to support thedevelopment and management of the current level of RCTs in the UKCRN ClinicalResearch Portfolio and the planned expansion of this activity over the next 3 years.

The role of CTUs within the evolving UK clinical research environment will becomeincreasingly important over the next few years to ensure that large, complex studiessuch as RCTs are appropriately designed and effectively coordinated.

Whilst the current disease/health research interests of the registered CTUs appears tobe well distributed, both geographically and in relation to the balance of RCTs within thecurrent UKCRN Clinical Research Portfolio, the current core staff resources in theregistered CTUs appears to be sub-optimal in relation to the number of RCTs theseCTUs are involved in coordinating. Furthermore, a significant proportion of current coreCTU resources are considered potentially unstable. These core CTU resources areexpected to be further stretched by the anticipated expansion of RCTs in the UKCRNPortfolio over the next 3 years.

In order for CTUs to effectively meet current and future demand for their expertise,existing CTU core resources need to be strengthened and expanded in parallel with theplanned increase in the number of RCTs in the UKCRN Clinical Research Portfolio.Without this expansion, there is a clear risk that, despite the recent substantialinvestment in project funding and NHS clinical research infrastructure, new, high qualityRCTs will not be developed at the rate expected and may fail to be successfullydelivered due to lack of expert oversight. This review was set up to assess the likelydemands on the registered CTUs over the next 3 years and provides the data forfunders to consider what action is needed to underpin the expansion of CTU activityrequired to support the increase in clinical trials.

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APPENDIX 1: UKCRC CTU Registration

Full Registration

In order to obtain Full Registration status, CTUs were required to demonstrate:

A track record and experience of coordinating multi-centre randomised controlledtrials or other well-designed studies

Presence of a core team of expert staff to develop studies

Presence of robust quality assurance systems and processes to meetappropriate regulations and legislation (e.g. the principles of Good ClinicalPractice, the NHS Research Governance Framework, the Data Protection Actand the UK regulations that implement the EU Directive for Clinical Trials)

Evidence of longer-term viability of capacity for trials coordination and thedevelopment/maintenance of a trials portfolio, including core funding or evidenceof a rolling programme of grants, with evidence of commitment from the hostinstitution.

CTUs which were already accredited by the National Cancer Research Institute (NCRI)for the conduct of multi-centre cancer clinical trials automatically became eligible for FullUKCRC Registration provided that they agreed to commit to the UKCRC RegisteredTrials Units best practice principles:

A commitment to working with UKCRN to support clinical research, e.g.contribution to national CTU committees and working groups

A commitment to providing study information and monthly accrual data to theUKCRN Portfolio Database for UKCRN portfolio studies

An organisational commitment to patient/public involvement.

Provisional Registration

It was recognised that some new and evolving CTUs may be developing relevantexpertise and experience that is worth building on, but that these CTUs may not yetmeet all of the criteria for Full Registration status. Therefore, evaluation criteria forProvisional Registration were developed which recognised CTUs that are clearlyworking towards possessing sufficient experience and expertise to obtain FullRegistration. CTUs were granted Provisional Registration only if they were able todemonstrate evidence of the competencies for Provisional Registration.

Full details of evaluation criteria for full and provisional registration criteria can be foundon the UKCRC Registered CTUs website7.

CTUs Awarded Full UKCRC Registration

1. Birmingham Clinical Trials Unit (University of Birmingham)

2. Bristol Randomised Trials Collaboration (University of Bristol)

7 www.ukcrc-ctu.org.uk/CTURegistrationProcess/Pages/KeyCompetenciesEvaluationCriteria

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3. Cancer Clinical Trials Unit Scotland (CACTUS) (ISD Cancer Clinical Trials Team,Edinburgh and Cancer Research UK Clinical Trials Unit, University of Glasgow)

4. Cancer Prevention Trials Unit (Barts and The London School of Medicine andDentistry, London)

5. Cancer Research UK & UCL Cancer Trials Centre (University College London,London)

6. Cancer Research UK Clinical Trials Unit (University of Birmingham)

7. Centre for Healthcare Randomised Trials (CHaRT) (University of Aberdeen)

8. Children’s Cancer and Leukaemia Group (CCLG) (University of Leicester)

9. Christie Clinical Trials Unit (Christie Hospital, Manchester and MRC Clinical TrialsUnit, London)

10. Clinical Trials Research Centre (University of Liverpool)

11. Clinical Trials Research Unit (University of Leeds)

12. Diabetes Trials Unit (Churchill Hospital, Oxford)

13. Edinburgh Clinical Trials Unit (University of Edinburgh and NHS Lothian HealthBoard)

14. Glasgow Clinical Trials Unit (University of Glasgow)

15. Institute of Cancer Research Clinical Trials & Statistics Unit (The Institute of CancerResearch, Surrey)

16. Medical Research Council Clinical Trials Unit (London)

17. Medical Research Council General Practice Research Framework & UniversityCollege London Primary Care & Mental Health Clinical Trials Unit (London)

18. Newcastle Clinical Trials Unit (Newcastle University)

19. North Wales Organisation for Randomised Trials in Health (NWORTH) (University ofWales, Bangor)

20. Oxford Clinical Trials Research Unit (University of Oxford)

21. Oxford Clinical Trials Unit for Mental Illness (OCTUMI) (University of Oxford)

22. Peninsula Clinical Trials Unit (Peninsula College of Medicine & Dentistry, Plymouth)

23. Pragmatic Clinical Trials Unit (Barts and The London School of Medicine andDentistry, London)

24. University of Southampton Clinical Trials Unit (University of Southampton and MRCClinical Trials Unit, London)

25. Wales Cancer Trials Unit (Velindre Hospital, Cardiff)

26. Warwick Medical School Clinical Trials Unit (University of Warwick)

CTUs Awarded Provisional UKCRC Registration

1. Clinical Research & Trials Unit (Norfolk and Norwich University Hospital)

2. Clinical Trials and Evaluation Unit (University of Bristol)

3. International Centre for Circulatory Health Trials Unit (Imperial College London,London)

4. National Perinatal Epidemiology Unit (NPEU) (University of Oxford)

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5. Northern Ireland Cancer Clinical Trials Unit with Northern Ireland Clinical ResearchSupport Centre (Belfast City Hospital and Royal Hospitals, Belfast)

6. Northern Ireland Clinical Research Support Centre (Royal Hospitals, Belfast)

7. Nottingham Clinical Trials Support Unit (University of Nottingham)

8. Oxford Respiratory Trials Unit (Churchill Hospital, Oxford and MRC Clinical TrialsUnit, London)

9. Oxford Vaccine Group (University of Oxford)

10. Primary Care Clinical Trials and Research Unit (University of Birmingham)

11. Sheffield Clinical Trials Research Unit (University of Sheffield)

12. South East Wales Trials Unit (Cardiff University)

13. The Keele Primary Care Musculoskeletal Trials Unit (Keele University)

14. York Trials Unit (University of York)

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APPENDIX 2: Geographical distribution of All Registered CTUs

Birming-ham

Edinburgh

Glasgow

NewcastleBelfast

Bangor

Leeds

Man-chester

Liverpool

Warwick

Oxford

London

Southampton

Plymouth

Cardiff

Bristol

Leicester

Fully Registered CTU

Provisionally Registered CTU

Norwich

Aberdeen

Stoke

York

Nottingham

Sutton

Sheffield

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APPENDIX 3: Geographical distribution of UKCRC Registered CTUs according to disease research interest

BLOOD CANCER

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CARDIOVASCULAR CONGENITAL ABNORMALITIES

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DEMENTIAS & NEURODEGENERATIVE DISEASE DIABETES

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EYE GENERIC HEALTH RELEVANCE

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INFECTION INFLAMMATION & IMMUNE SYSTEM

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INJURIES & ACCIDENTS MEDICINES FOR CHILDREN

59

MENTAL HEALTH METABOLIC AND ENDOCRINE

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MUSCULOSKELETAL NEUROLOGY

61

ORAL & GASTROINTESTINAL PRIMARY CARE

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RENAL & UROGENITAL REPRODUCTIVE & CHILDBIRTH

63

RESPIRATORY SKIN

64

STROKE OTHER

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APPENDIX 4: List of Other Sources of CTU Core Staff Funding

The following were also listed by CTUs as a source of funding for core staff roles.

Biomedical Research Centre Cephalon Fellowship Charity (not specified) Christie Charitable Funds DH Fellowship Foundation for Circulatory Health Friends of the Cancer Centre Lymphoma Research Trust Marie Curie Cancer Care NCCRCD Fellowship Northern Ireland Blood Transfusion Service NIHR National School of Primary Care Research Wellcome Trust

APPENDIX 5: List of Other CTU Staff Roles

The following were also listed by CTUs as core staff roles which were not classifiedunder the main core staff role categories associated with the design and delivery ofRCTs.

Clinical Trials Pharmacist Education Programme Staff Laboratory Staff Medical Writer Research Nurse Research Practitioner Research Technician Systematic Reviewer Translational Research Scientist

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APPENDIX 6: List of organisations funding five or fewer UKCRNPortfolio RCTs

1. Action Medical Research2. Addenbrooke's Charities3. Alcohol Education and Research

Council4. American Institute for Cancer

Research5. Asthma UK6. Australian MRC7. Breakthrough Breast Cancer8. Breast Cancer Campaign9. Breast Cancer Research Trust10. British Lung Foundation11. British Society for Blood and

Marrow Transplantation12. British Society of Paediatric

Endocrinology and Diabetes13. British Thoracic Oncology Group14. Broad Foundation15. Canadian Institute of Health

Research16. Charles Wolfson Charitable Trust17. Chest, Heart and Stroke Scotland18. Child Growth Foundation19. Children’s Cancer & Leukaemia

Group20. Celecoxib Oncology Research in

Europe21. Cystic Fibrosis Charity (US)22. Dunhill Medical Trust23. East Anglia Thoracic Society24. European Blood and Marrow

Transplant Group25. European Science Foundation26. European Union27. Food Standards Agency28. Groupe d'Etude des Lymphomes

de l'Adulte29. Health Department of Western

Australia30. Heart Research UK31. Henry Smith Foundation32. International Breast Cancer Study

Group33. International Extranodal Lymphoma

Study Group34. June Hancock Mesothelioma

Research Fund35. Juvenile Diabetes Research

Foundation36. Kidney Research UK37. London Lung Cancer Group

38. Lymphoma Association39. Lymphoma Research Trust40. Multiple Sclerosis Society41. Multiple Sclerosis Trust42. National Blood Service43. National Council for Research, Italy44. National Health and Medical

Research Council of Australia45. National Heart Foundation of

Australia46. National Kidney Research Fund47. National Lottery48. National Osteoporosis Society49. National Prevention Research

Initiative50. Newborn Appeal51. Orchid Cancer Appeal52. Parkinson’s Disease Society53. Remedi54. Rosemere Cancer Foundation55. Royal College of Physicians56. Scottish Executive57. Scottish Gynaecological Cancer

Trials Group58. Southern European Urological

Group59. Swiss Institute for Applied Cancer

Research60. The Alzheimer`s Society61. The Castang Foundation62. The Hypertension Trust63. The Prostate Cancer Charity64. The Stanley Medical Research

Institute65. US National Heart Lung and Blood

Institute66. US National Institute of Health67. Wales Office of Research and

Development68. Welsh Assembly Government69. WHO (Uganda)70. World Cancer Research Fund

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