Technology Innovation Centres

Appendix C Best practice models for translational research centres in medical technologies

A Joint Loughborough University - University Hospitals of Leicester MRC IDBA International Innovation Workshop, ABHI, London 23 January 2008

Introduction

It is becoming recognised that there is an international requirement to create translational research centres in medical technologies. Such centres of excellence will work by integrating clinical professionals, industry and academia and are targeted at generating practical improvements in human health and business opportunities. This will be achieved by enabling the systematic research needed to translate inventions into practical technology platforms which have the potential to be exploited to the benefit of patients and the businesses which can produce them. This in turn will further enhance national and regional economic activity progressing national and regional innovation agendas and enhancing the role of healthcare provider organisations as an engine for regional economic growth.

The purpose of the workshop was to share best practice nationally and internationally to explore the essential strategies for success in the development of such centres of excellence and to have a timely influence on UK policy.

The workshop formed part of the work of the innovation strand of the Joint Loughborough University/University Hospitals of Leicester NHS Trust MRC funded Interdisciplinary Bridging Award (IDBA).

The core of the meeting was formed from presentations by Dr Mark Beggs, Programme Manager of the Wyeth Translational Medicine Research Collaboration (TMRC), Dundee, and Dr Alan Russell, Director of the McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Centre, and the ensuing discussion. This note summarises the presentations and discussion, including some subsequent to the meeting. Attendees are shown in the appendix.

During the meeting Jill Dhell gave an update on the status of the National Institutes for Health Research (NIHR) stemming from "Best Research for Best Health" and of the two pilot Healthcare Technology Co-operatives (HTC) linking academia, business and clinicians, indicating that they were to be announced in the next few weeks. Each HTC is to be provided with core funding of £275k p.a for two years and is aimed to prime infrastructure for medical technology research in areas of unmet clinical need, centred on the patient. The role of the topic-specific research networks, and the UK Clinical Research Collaboration and associated networks was also noted.

Data on two other examples of significant internationally recognised translational medicine centres, The Langer Lab at MIT and the Translational Centre for Regenerative Medicine in Leipzig, were also tabled.

Translational Medicine Research Centre at Dundee, Mark Beggs, Wyeth

Mark’s presentation began with an explanation of the motivation for the Dundee Centre. A major problem for the pharmaceutical industry is the very high level of product attrition rates that occur within Phase 2 clinical trials, which continues to worsen. Wyeth believe that the development and application of bio-markers which can be used for drug discovery and development will decrease attrition rates through the product pipeline. They see the key to success in the creation of TRMC as being an appropriate combination of academic research, NHS involvement and industrial collaboration. All parties bring different sets of attributes, which when combined help overcome the major impediments to the development of new bio-markers.

The TMRC model involves four universities (Dundee, Aberdeen, Glasgow and Edinburgh) as well as 4 NHS Trusts, Scottish Enterprise and Wyeth each with complementary skills. The latter contributes $8m via operational funding and $45m via research contracts and Scottish Enterprise provide $35m; half as an R&D grant on the basis of a 5-year renewable award and half as a loan. Having a defined time limit focuses minds upon successful delivery. The TMRC acts as a hub for the translational community.

Governance of the collaboration is important as this is not a grant funding scheme nor is it as rigid as contract research. Full economic costs are paid to academia and any resulting IP is assigned across the collaboration partners depending on its application. The initiative represents a balanced middle road to collaboration where all parties receive mutual benefit.

The mechanics of the scheme involve ideas being jointly generated by the company and the Principal Investigator (PI), which are then peer reviewed by the PI and his or her opposite number in Wyeth – to ensure strategic business fit – followed by further review by the TMRC. Project costs are paid for by Wyeth and infrastructure support by Scottish Enterprise. To allow for flexibility, research plans may be modified to the mutual agreement of all parties. IP is jointly owned via a complex model which permits academic publication subject to prior protection.

The dedicated Core Laboratory base in Dundee acts as an analytical centre of excellence for the four Universities and is run as a central service with the extremely high quality standards required for exploitation. The Core Laboratory is also responsible for all ethics and governance control as well as ensuring that all base data are collected and handed over at the end of a project. It focuses on the development of platform tools and technologies including genomics, proteomics, assay development, bio-statistics and informatics. By 2011 deliverables expected include, from the commercial perspective: IP development, economic growth, new diagnostic tests, earlier diagnosis of disease and an increase in the number of novel therapies. From a research perspective, highly cited publications and the development of new research areas and topics will be key outputs.

Immediate discussion that followed centred on the issue of state aid, and the reasons why Wyeth had chosen Scotland. Responses to the latter included the readiness of the Scottish network and its geographic concentration, the historic familiarity with clinical trial work in Scotland due to certain disease prevalence, the relative simplicity in progressing discussions and the availability of electronic patient identification in Scotland.

McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Centre, UPMC, Alan Russell

The presentation began with the background to the development of the UPMC and the economic regeneration of the former steel town. A great deal of the city’s wealth is now generated as a direct consequence of the prowess of its universities (Duquesne, Pittsburgh and Carnegie-Mellon) including their interaction with the health industry. The UPMC has undergone significant growth since its foundation as an academic medical centre in the early 90’s. It is now one of the largest medical systems in the US (22 hospitals) and has an operating margin of around 5% on a revenue of more than $6bn. As a consequence it is able to partner with industry and business – it makes deals rather than behaving as a mere sub-contractor. UPMC is now the sixth largest recipient of NIH funding ($375.8m) and has some 1,800 faculty members. It has been working in regenerative medicine for twelve years and in 2000 it visibly established its focus via the McGowan Institute with the sole passion to bring new regenerative technologies to its patients as quickly and as safely as possible – clinical translation. Importantly, McGowan will apply other peoples work too. UMPC pump primed McGowan at a significant level ($3-5m). It is important to recognise that this focus has also enabled significant success in for example spin out (14) and job creation (~470) for the region. It also has 10-15 clinical trials in progress and significant Department of Defence funding. While McGowan includes 215 faculty across the region, one third of whom are clinicians, the core of McGowan is 35 faculty located in two new buildings – income to the core faculty is around $15m per year with $73m to the wider organisation.

The success of the UPMC and the McGowan Institute can be directly attributed to the level of its interdisciplinary research, many of the successes would not have been achieved without different disciplines learning how to effectively work together whilst remaining focused on a common goal. This requires a critical mass of individuals/expertise and getting people to work together. Consequently a focus on clustered teams has been a priority from "day one". It was emphasised that interdisciplinary work is unnatural and that traditionally academics are happy to work in their individual silos, it requires behavioural change and the resetting of clinical ambitions (by buy-outs for research). Alan emphasised the work of McGowan was sited in Pasteur’s Quadrant – that of value laden use inspired basic research (see Donald Stokes, Pasteur’s Quadrant: Basic Science and Technological Innovation, Washington DC: The Brookings Institution, 1997) – in effect representing the journey from bench to bedside and back, translational medicine.

Alan highlighted the key lessons learnt in successfully establishing the Institute. These included: the need to secure commitment from individual academics and groups of academics which then enables these to be linked together; the activity must take place on a large scale ($10m is a minimum to make an impact, in reality >$50m is required); individuals need to be 100% committed to the concept of interdisciplinary working and "fakers", non-collaborators just in it for the funding, are rooted out early; the focus has been objective driven (patient-focused). Additionally, the whole working environment and related "hygiene factors" need to be excellent, there has to be sufficient "foundations and scaffolds" for individual groups to build their "castles". He reinforced the need for bottom up buy-in, empowered leadership top down facilitation and management, clear management structures, the need for a mixture of central dedicated facilities and the ability to offer appropriate incentives to staff to facilitate their participation. A common barrier to facilitating interdisciplinary research is an existing negative culture and overly complex tiers of bureaucracy/hierarchy. Some level of project failure is to be expected and encouraged if internationally leading and valuable work is to be carried out. Inter-institutional collaborations are also not without problems: for example, an attempt to use common IP terms and conditions in contracts between institutions have not worked in Pittsburgh.

He closed by saying that the Institute and the UPMC wish to export their model and are establishing some other worldwide translational science centres, including one in Palermo, Sicily at a cost of EURO 350M. They also have aspirations to perhaps establish similar centres in Ireland and the UK. UPMC will undertake management, under contract, of a hospital facility in the UK in the near future.

Following the presentation, discussion began with questions on the McGowan model but subsequently broadened to other areas. In summary it included the following:

· Research on a large scale is essential because of critical mass requirements and a pragmatic recognition that at least 30% of activity will never generate the anticipated outcomes. True solutions only tend to be found where a significant level of activity is duplicated between competing groups. The $50m threshold for work of value requires identified leadership, the scientific and business/economic case for the particular field and influencing at the right level of government. The evidence for the business/economic case is both the hardest to generate and to evaluate. Any business case is likely to be phased.

· It would be of value to have a more extensive survey of the different models of translational research centre to assist in the preparation of business cases for any UK initiatives.

· The importance of physical/regional co-location and joint working of a core was also emphasised as evidenced by both models – being there must be part of the daily work of the people. Choosing the full time team is also critical. This challenges some of the current UK emphasis on networks and committees of involved but not committed stakeholders.

· Often the initial ideas for such institutes occur bottom-up in an informal setting and are usually only taken forward successfully where a charismatic leader exists. The leader must build a persuasive scientific and business/economic case and give directional leadership to the emerging enterprise. The operational details then follow. The theme of such an institute, the "big idea", will inevitably match a local need but resonate at a larger scale, embrace risk and probably "change the rules".

· It was acknowledged that within the UK there is a growing national and regional recognition of the need to think bigger, as has been evidenced in recent aerospace and energy initiatives. Large institute models are under consideration for a national nanomedicine initiative. The importance of developing national and regional "joined up thinking" between individual RDAs, the Research Councils, the Technology Strategy Board, industry, the NHS and universities was emphasised.

David Williams, Oliver Wells and Peter Townsend, February 2008

Attendees at IDBA Innovation Workshop ABHI, London 23 January 2008