Condemnation of the New Zealand Terrorist Attacks

This morning I woke up to the unfolding story of a terrorist attack on people at prayer in mosques in Christchurch, New Zealand. While this blog is usually focussed solely on my thoughts on medical device and health technology innovation, today's events feel like a "wake up" call to all those who stand against the hatred that drives terrorists of all persuasions. In my work I am surrounded by ample evidence that the lies these extremists (and their supporters) peddle to justify these atrocities are just that, lies. 
Here at Sheffield University, I know that all my colleagues and students are proud of our diversity on all levels, diversity of nationality, race, gender, and most of all today religion. This diversity underpins our ability to investigate, understand, and ultimately solve the major challenges facing the world today, not least in the field of oral health and innovation where we focus the endeavours of the Dental School.  To make my own small contribution to this important goal, I am fortunate to work closely with a large number of PhD students and visiting academics, many of whom hold senior research and clinical positions in universities throughout the world. These include Muslim academics from Kuwait, Iran, Iraq, Saudi Arabia, Malaysia, Pakistan, Bahrain, and the UK. Irrespective of background, we are united in our efforts to undertake research for the benefit of humanity and the world, we share the same values, and - more widely - we believe in cooperation to find peaceful solutions to the complex challenges that face humanity at the beginning of the 21st century. These are facts.
People that believe any one race or religion are especially prone to extremist ideologies are at best ignorant, or far worse they are deliberately peddling a hateful narrative to achieve their own political or economic goals. Examples of the latter are already espousing lies and bigotry (just look at the statement of Australian Senator Fraser Anning if one needs an example, sadly others exist). The atrocity in New Zealand - following a long series where different religions have been the victims - demands a response to all extremists and their poisonous ideologies, irrespective of the identity they and their supporters claim to hold. This post is my contribution to challenging the lies peddled by racists and extremists who fuel violence and terrorism.

Annual Research Meeting of the School of Clinical Dentistry: Report

This year the format for our annual meeting was changed, firstly to celebrate 10 years since the official opening of our (then) new Research Wing by Professor Sir Mark Walport, and also to incorporate a Festschrift for our former Dean Professor Paul Speight.  We were welcomed to the event by Professor Dame Pamela Shaw, Vice President of the Faculty of Medicine.

In my opening address, I emphasised the importance of oral health research, in particular the scale and diversity of current challenges ranging from poor cancer survival rates through to the negative impact of common dental diseases on quality of life. These are not abstract problems; in addition to human suffering, oral health challenges have a major impact on the UK economy through lost working hours and poor school attendance, as well as direct costs to the NHS. For these reasons, the School of Clinical Dentistry works closely with both healthcare providers and industry to carry out research of the highest standard to better understand the major challenges in oral health, and so to develop better therapies, technologies, and interventions. Moreover, our researchers go beyond  “discovery science” to investigate the impact of poor oral health on patients and societies, and to identify effective tools to better motivate individuals to take responsibility for their personal oral health. 

It was noted that since the opening of the research wing in 2008, we have published over 1100 full papers in peer reviewed journals, graduated 127 PhDs (with over 50 currently studying for a PhD), and received over £11million of research funding, confirming our place as a world leading centre for oral and dental research. I concluded my presentation with a brief review of our extensive industrial collaboration, and explained how UK Industrial Strategy represented an important opportunity to highlight to government the positive impact of our research on innovation and economic growth.

We were therefore delighted that Dr Steve Mason, the Medical Director for Oral Health at GSK, accepted our invitation to provide a keynote address on industrial drivers of research. He gave a superb overview of their work and current research priorities, as well as insights into deeper strategic thinking and the importance of research ethics to GSK. Given the importance of UK Industrial Strategy in shaping future research funding, a greater understanding of where academic, clinical, and business priorities align is important in developing a coherent message for the new UK Research Office (UKRO).

Other sessions focussed on our research excellence, with talks based on some of our very best “4*” publications, our multidisciplinary collaborations that included work with industry and the NHS, and the positive impact of our research via either the translation of science from the laboratory to a clinical setting or improved interventions for patient and societal benefit.  These sessions collectively emphasised the tremendous multi-disciplinarity of our research community, and the range of healthcare challenges where we had already made a positive difference to quality of life.

Day One ended with a Festschrift for Professor Paul Speight, not only our former Dean but also a world leading clinical researcher and pathologist.  His status as an internationally leading oral pathologist, and the importance of his personal research, were very evident from a series of talks from individuals who had studied under Paul and gone on – inspired by him – to become eminent themselves.  Speakers included Professors David Moles, Paul Brocklehurst, John Marshall, and Richard Jordan who had travelled all the way from San Francisco. In addition Paul’s demonstrable scientific and clinical contributions, the importance of more human elements in research success were made very clear by all the speakers at this Festschrift, including inspiration, high standards, integrity, respect, and friendship.  This theme continued with our celebratory dinner at the Cutlers Hall.

Day two of the meeting was given over to the School’s early career researchers and PhD students to show their considerable talent and ability. The standard was exceptionally high, and this was a timely reminder that a research environment relies heavily on hard working, bright and motivated clinical and non-clinical postdoctoral staff and students.  While all of the talks and posters were excellent and it was therefore difficult to agree on the award of prizes, a number were eventually selected. Congratulations to the prize winners: Ashley Towers for his talk on virtual reality in dental education, Areeg Elmusrati and Mariam Khokhar who shared the poster prize, and Katharina Clitherow for the popular “Gone in 60 seconds” presentation where she used a video animation to explain research into adhesive patches for drug delivery to oral soft tissues.

Overall this was a superb research meeting, certainly one of the best the School has put together, and it provided a good opportunity to reflect on the distinctive work of our multi-disciplinarily community.  This reflection is important, as it helps to (re)define both our internal priorities as well as how to  best showcase our work for an external audience.  My view is still that the wider world - including elements within universities, government, and the media - do not really understand oral health and the important research conducted by the leading UK dental schools.  Without understanding either the challenges or the benefits of our excellent research (to the economy as well as patients and society), it is difficult for them to make sound decisions with respect to funding priorities.  It is vital then that we use the lessons from our Annual Research Meeting to communicate the importance of our work even more effectively.

Despite these personal concerns, I am encouraged that there are also many senior figures who do appreciate the multi-disciplinarity of our research, as well as the complexity of challenges in oral health and as its connectedness to wider issues. Professor Sir Mark Walport, the head of the new UK Research Office that will be very influential in shaping national investment for the foreseeable future, opened our “new” wing in 2008.  He very kindly sent the School a personal message in recognition of this 10 year celebration, and I quote from it here:

“Many congratulations on the 10^thAnniversary of the opening of your research wing.  It was my hope when I opened the wing in 2008 that it would allow Sheffield to build on its excellent record in dental research, and it’s evident that this has come to fruition….Congratulations also on your excellent work at Sheffield – you are focusing on publishing research of the highest quality and collaborating with external partners to maximise the impact of this research. You have an important role to play in communicating the importance of oral health research.”

I believe that UKRO will bring many benefits by better integrating the different sponsors of research in the UK (primarily the Research Councils and Innovate UK).  Given that our community is truly multi-disciplinary, and the problems we are addressing frequently span social science, medicine, and engineering, any improvements in the coordination of funding for interdisciplinary research will be good for oral health research. The challenge for us now - not just at Sheffield but also in all leading UK Dental Schools and with our industrial partners - is to even more effectively communicate the importance of our research for the benefit of UK society and the economy.This year’s annual research meeting is an important part of the process that will inform both our thinking and planning at Sheffield.

Overcoming Adoption Challenges in Healthcare for Societal Benefit

BIN@Sheffield2017 Meeting Report

The Business Innovation Network (or BIN) is holding its annual meeting in Sheffield this week. This is an unusual event in that it seeks to stimulate economic growth and wider societal benefits by harnessing the specific-but-often-disparate strengths of a city and region, in particular the academic base. I had the privilege of attending a morning dedicated to medical, dental and social challenges, and chaired the session on overcoming barriers to adoption in healthcare. My experienced speakers - who kindly  also formed a panel for a lengthy Q&A session - were Keith Jackson (CEO of 8-Q and former MD of JRI Ltd.), Jason Brannan (Communications Director for Y&H Medilink), and Fernando Monteiro (Professor of Biomedical Engineering, University of Porto).  While some of the more obvious issues were raised and discussed, there were also some points that were less predictable and therefore worth capturing on this blog.  Those that struck me included:

• Regulations are essential for patient protection and a cornerstone of responsible innovation. While the new medical devices regulations were undoubtedly going to stress our industry (with a heightened risk of losing businesses that manufacture excellent products), there were also some benefits beyond increased patient safety. Firstly, innovation would need to make a demonstrable difference before it could be placed on the market. Secondly, the new regulations also presented new business opportunities. My previous two blog posts deal with the new regulations and responsible innovation.

• One good example of an emerging business opportunity is the translation of in silico modelling for use as a real tool for validating medical devices or drugs as a part of a comprehensive pre-clinical screening and testing programme. Tremendous academic progress has been demonstrated by groups such as Insigneo in Sheffield, but the attractiveness to industry of this work will be increased by the inclusion of modelling in the new medical devices directives (and parallel developments at the FDA).  The development of sound, validated modelling tools will therefore assist both the development of healthcare technologies and their passage to the market.

• The final point made by the panel was that it was possible that some contemporary healthcare solutions were potentially over-engineered (and therefore costly). New approaches were needed to determine which solutions were “good enough” in terms of delivering a satisfactory and cost-effective result without compromising quality of life. The innovation community is already complex, but there is a case for bringing together even more multi-skilled teams to tackle challenges that have reached new levels of complexity.

Wider changes and the huge scale of the healthcare challenge suggests that societies will need to find new ways of covering the costs (and risks) of translating from the laboratory to the clinic.  Multi-disciplinary partnerships with private and public sector entities will be increasingly attractive as a means of sharing risks and costs, with some degree of government engagement and involvement. These could be all the more successful if city and regional councils can work together to strengthen the environment or “place” where innovation is developed and tested.  We will perhaps see the rise of new not-for-profit entities to act as umbrella organisations that address the more complex healthcare challenges. City regions that best understand and support these changes will benefit from the high value jobs and economic growth that the healthcare industry will deliver.

The UCL Special Inquiry into Regenerative Medicine Research

University College London (UCL) has published the findings of a Special Inquiry into Regenerative Medicine Research, a lengthy document that seeks to understand the role of one of the UKs foremost research institutions in the rise and subsequent fall of Paolo Macchiarini. By way of brief background, Macchiarini was considered to be a leading researcher and pioneering surgeon in the field of regenerative medicine for tracheal and airway "tissue engineering" until a series of troubling revelations - associated with several tragic deaths - culminated in his public exposure in 2016.  Many aspects of the story, especially the role and personality of Macchiarini himself, have been covered by the media (including social media), and it is clearly a complex scenario. Macchiarini could not though have achieved his notoriety alone, indeed he became an internationally respected figure in the wider tissue engineering community, and the UCL report provides a substantial insight into how senior academics and hospital clinicians became associated with him personally and professionally.  The report is especially compelling as it has been written by some of the UK's leading academics and clinicians with an international reputation for excellence and probity including in the broad field of tissue engineering and regenerative medicine (TERM), and who have had access to at least some key documents and people. This makes it a more reliable document than some previous media reports, as well as essential reading for all researchers in the TERM field (as well as bioethicists, lawyers, and clinicians more generally). Inevitably though while resolving a number of issues, it also raises questions where more information is needed, and perhaps some of these unanswered questions could only be resolved in a legally empowered inquiry. Before considering these though, it is important to bear in mind the following:

• TERM is a broad field that is largely concerned with the development of therapies that promote the successful healing of human tissues in situations where this would not otherwise occur naturally.  While more research is needed, it is a field that offers potential solutions where current clinical interventions are either limited or do not exist.  Many thousands of scientists, engineers and clinicians are engaged in sound and responsible research all over the world (including at UCL), and in parallel other experts including regulators and industries are working equally hard to reduce risks while bringing benefits to patients.  The Macchiarini story is not a reason to curtail this activity, but it is essential that it informs practice, especially proper governance in responsible translation to the clinic.
• The clinical cases covered by this inquiry involved sometimes subtly different interventions, and this diversity is greater when considering all of the surgical procedures where Macchiarini was involved outside of the UK. When patients die, this is always a tragedy for them and the families left behind. Even if interventions were classed as palliative, this does not negate questions related to the governance of an experimental medical procedure and informed consent (questions that lay largely outside of the scope of this inquiry, but questions that should arguably be now addressed using a robust instrument).

While UCL's report on the special inquiry is both detailed and insightful, it also recognises the scale and complexity of investigating experimental clinical interventions involving more than one organisation (and therefore the limits to this type of investigation). The subject of the inquiry was the primarily the role of UCL staff in forming a relationship with Paulo Macchiarini (including the award of an honorary chair), and the role of the institution in a series of operations that sought to apply experimental TERM-like technologies in human tracheal/large airway surgery. In places the inquiry also considered interactions between academic and clinical staff, and aspects of local compliance with legal, regulatory and governance requirements.  In my experience of working in a mixed clinical-basic science environment, senior staff understand very clearly which organisation they work for (it is printed on their payslip), and also to whom they are responsible to when working (which could be an NHS Trust), irrespective of the honorary contracts they hold. In simple terms, if a clinician is treating a patient, they are responsible to the relevant NHS Trust irrespective of which organisation is printed on their personal payslip. Likewise it is the NHS organisation governance that applies when treating patients, irrespective whether the intervention is established or experimental.

Outside of the remit of this report lie a number of as yet unanswered questions. For example is the current legal, regulatory and ethical framework fit for purpose, and if "yes" then were established legal/governance processes and procedures accidentally or deliberately bypassed in some clinical cases covered by this inquiry (and indeed others around the world)? While my experiences suggest that our existing legal and regulatory framework is both robust and fit for purpose, this is a question that can only be addressed fully by a wider pool of experts (including in law, ethics and regulatory affairs). It is also a question that is arguably more pertinent to the hospitals concerned rather than their associated universities, and it seems therefore likely that this UCL report is only a first step towards gaining a better understanding of these events in the UK and beyond.

New European Medical Devices Regulations: Implications for Innovation, Brexit and i4

The Medical Devices Directives are European laws that essentially govern the manufacture and sale of all medical devices - ranging from dental fillings to hip replacements and pacemakers - in the European Economic Area.  These have recently been overhauled for a variety of reasons, including better harmonisation with the regulatory environment for pharmaceuticals as well as in response to a number of disasters I have written about before (such as metal-on-metal hip replacements and the PIP breast implant scandal). No blog could be sufficiently long and detailed to cover the details of the new rules, but some key features of note are:

• The regulations are more comprehensive and demanding in almost every way, meaning more details are recorded (from the supply chain, placement in the patient, and at the point of failure). The level of detail is greater, and the depth and rigour of the quality assurance processes being applied has been increased substantially.
• With resect to traceability, the vast majority of medical devices will now have a unique identifier so that they can be followed on a supply chain "time line" from manufacturer to patient to failure.  Some devices will most likely be exempt, for example dental materials, but for the first time so-called cosmetic devices (such as breast implants) will be captured by the new regulations.
• Patients will benefit from an "implant card" that describes their new device, the risks, and alternatives, all in theory written in lay terms.
• Post-market surveillance will be strengthened substantially, and communication between different European countries will be greatly improved.
• Manufacturers will need to employ and identify a named competent person to oversee and take personal responsibility for the quality assurance of their products and compliance with the Medical Devices regulations.

While many campaigners will see these changes as good and probably long overdue, there will inevitably be some more negative consequences.  Most obviously, tougher regulations will introduce new costs into the manufacturing process and the healthcare system, and these costs will ultimately need to be covered (with the most simple mechanism being a price rise that we will all pay for in one way or another).  There are, however, a number of impacts that are more difficult to predict.  For example, the scale and complexity of the regulations means that smaller companies might struggle to comply - especially with innovative products - and instead it is likely the new regulations will on balance favour the larger multinationals who have the critical mass and expertise to manage these changes internally.  This may not appear as a "negative" to the casual reader, but there is evidence that a proportion of innovation that is destined to be valuable for patients (in terms of reduced pain or enhanced quality of life) takes place in smaller companies (so-called SMEs).  I am therefore concerned that some aspects of the new regulations could work against the product innovations we all need, and patients will suffer and/or have shortened lives as a result. This may though be a price worth paying for more responsible innovation, especially in sectors such as regenerative medicine where there is an emerging narrative suggesting that experimentation on patients without proper informed consent may have occurred.

There are countless examples of unmet clinical needs. Just one increasing challenge is device-associated deep bone infection.  The costs associated with this problem are huge, the pain and misery for the patients is very real, and the consequences for society are serious.  There are many promising solutions that could address this challenge being worked on throughout Europe (including in my laboratories), and the most promising technologies are already being passed to companies for commercial assessment. There is a real risk that, at the time of greatest clinical need, we will raise the regulatory barrier so high that their development ceases to be clinically or commercially viable.

Not all aspects of the new regulations are negative; indeed I agree that the system needed a major overhaul, and the majority of changes are affordable and in the public interest. The possibility of small businesses failing and innovation being curtailed is a risk rather than a certainty, but one we should be aware of.  Of the many positive aspects, the most exciting is arguably the traceability of medical devices throughout the supply chain to the patient. Coupled to "i4"(the 4th industrial revolution where the level of detail and control of the manufacturing processes is being transformed),  there is an opportunity here to gain unparalleled insights into the factors that determine success (or failure) of almost every medical device placed in a person.

There is though one final dark cloud looming ... Brexit!  In my opinion, access to the European market for UK medical devices manufacturers is essential and non-negotiable. My reasoning is based primarily the huge value of this sector to the UK economy, and the specific value of European exports to most of our businesses. This will mean full UK compliance with the new regulations, but without a seat at the table to discuss their modification or improvement during this long but critical implementation phase.  Some Brexit supporters seem unable to grasp the potential social and economic costs of a failure to negotiate a sound departure from the EU, and their first instinct is to be pleased to shake off the shackles of European laws, even laws designed to promote trade while protecting citizens. The changes to the Medical Devices Directives will have a real impact that should include safer materials and technologies for patients, but could include the loss of businesses and jobs in the UK if we do not manage their implementation carefully.

Emma Walmsley the CEO Designate GSK: Implications for Dental Research

The very recent announcement that Emma Walmsley is to replace Andrew Witty as CEO of GSK next March is both remarkable and welcome news. Remarkable because not only will she will be the first woman to lead a multinational pharmaceutical and healthcare "giant", but this is to the best of my knowledge the first time such a high profile position has been taken by somebody from the consumer health world.  Personally - as a father to two daughters and I hope a modernist on all matters related to gender and diversity - I am always delighted to see tangible evidence that the "glass ceiling" to women's career aspirations is being further eroded.  It is, however, the promotion of a member of the consumer healthcare community that is perhaps even more significant for dental research in the UK and beyond.

This appointment should of course not be surprising news. The 2015 turnover for GSK Consumer Healthcare was in the region of £6billion, 25% of GSK Groups total turnover. Emma has already led GSK Consumer Healthcare through a period of growth as well as part of a complex merger with Novartis last year, and it is important to note that a proportion of this business growth was related to investment in healthcare R&D leading to innovative high added value products that have been successful in a highly competitive market.  Oral health products are an important part of the GSK Consumer Healthcare portfolio, representing almost 1/3 of total sales in 2015.  To summarise then, GSK are a highly successful UK-based multinational, and they have appointed a new CEO with a strong track record in their consumer health division.  This information is all available in the press and indeed on the GSK web site, why is it significant for UK dental research and oral health?

Firstly, fluoride toothpaste is by far the most important consumer health product in the world.  While the reasons behind falling caries rates in the west are undoubtedly complex and include public education and excellent oral and dental healthcare systems, fluoride toothpaste is a key contributor to the generally excellent oral health enjoyed by many people throughout the world.  It is highly unusual for a consumer health product to have had such an impact on a non-communicable human disease.  Its success is seen not only among western populations, but also with the emerging middle classes in the developing world.  Trends in toothpaste innovation in recent years have moved on from caries prevention (where modern formulations are undoubtedly successful) to reducing tooth sensitivity (arguably a consequence of the success in preventing caries). However, there are still vast populations in the developing world where fluoride toothpaste use is minimal and caries rates are increasing rapidly.  There is an opportunity here for oral consumer healthcare companies to develop affordable products to deliver a real reversal in caries growth.  Even though caries rates have fallen in the west, there are still many opportunities for innovation to improve oral health here more generally too.  Tooth sensitivity, dry mouth, tooth erosion, periodontal health, and public education are all areas where the UK (and indeed the world) would benefit from more effective partnerships between healthcare providers, universities, and industry.  Most obviously, some of the differences between consumer health products and pharmaceuticals are increasingly blurred, and the opportunities for crossover between old divisions are very real.

My prediction is that Emma Walmsley may not produce radical changes overnight, but her appointment will see an increase internal communication within a highly structured business, and this will in turn facilitate even greater use of open innovation models to support R&D. Generally, this has to be a good thing for the UK's Dental Schools, but it means we may have to sometimes change in parallel to accommodate external business priorities.  The benefits will be that the UK will develop more productive consortia between industry, Dental Schools, and our colleagues in oral healthcare delivery. This increase in the quantity and quality of collaborative R&D will deliver greater health, societal, and economic benefits for the UK and the world.

Report on a scientific meeting: bone-tec 2015 (Stuttgart, 8th to 10th October 2015)

This blog is primarily for the benefit of my research group and collaborators back in Sheffield, but hopefully it might also shed some light on the purpose of scientific meetings for others who view these posts. With this in mind, in case you are not familiar, a scientific meeting is intended to bring the research community together to see and criticise each other's work, and to share ideas for future research that might result in scientific progress that in turn drives the development of new therapies. Many scientific meetings are huge, and while there are benefits in seeing the whole global family of biomaterials and tissue engineering in a single location, it can sometimes be a frustrating experience as the scale can inhibit the purpose.  This autumn I have been privileged to present at bone-tec, a much smaller meeting of around 100 people with a focus (quite obviously) on bone tissue regeneration. For me it has been a salient reminder of the benefits in attending a smaller, more focussed meeting compared to a European or World Congress.  Why is this the case?  The reasons are numerous but include the ease of attending only a single session (compared to dashing from theatre to theatre for different sessions), the opportunity to discuss current research with some of the world's leading scientists and engineers as well as PhD students and postdoctoral researchers.  Most importantly, you actually have the opportunity to give your full attention to an important field that will undoubtedly shape emerging new medical treatments in the forthcoming years and decades.
So what have I learnt, both generally and of use to my own group?  The bulk of the programme was centred on progress in the identification and use of small biological molecules that facilitate or accelerate the healing of challenging bone defects.  While some work considered the detailed mechanisms that underpinned the biological effects of known osteoinductive molecules (e.g. BMP2), other talks were on less well known but potentially important cytokines.  Many of these cell signalling molecules were related to inflammatory pathways and included several interleukins associated with early inflammation.  These papers collectively underlined the close relationship between inflammation and bone repair, and significant progress was demonstrated in what is still a complex and rapidly evolving field.  One other area that has grown recently is endochondral ossification and the potential use of hypertrophic cartilage (cells and/or matrix) to promote bone tissue healing.  While Sheffield-based academics have been engaged in this field for several years (in our early years, we were one of the few centres that recognised the potential value of these strategies), there is no doubt that today there are several major research teams making rapid and significant progress, and my view is that we are right to remain active in this specific field.  There were many other research themes covered where Sheffield has a track record including nanoscale ceramic gels where Richard Oreffo showed some very impressive laboratory models to evaluate their potential. My presentation on multi-functional materials that combined antimicrobial properties with promotion of bone healing attracted several questions and invitations to discuss collaboration.  I also saw a number of papers where it appeared that Sheffield might form useful partnerships, for example Jons Hillborn presented a particularly elegant study of delivery strategies for siRNA and related molecules that had considerable therapeutic potential (for example, in the treatment of cancers). As well as new data on biological compounds, a number of speakers covered innovations in bioceramics and bioglass research, and there is no doubt this field continues to evolve and will most likely see new clinical products in the near future. The hosts provided an impressive talk on the application of Raman to detection of mineral in tissue culture, a little too late for us to form a collaboration but very encouraging nevertheless.   In addition to a large number of high quality academic and clinical speakers, we also heard from industry. One notable speaker was from the company PreSens who have a wide range of non-invasive sensors to detect changes in in vitro systems including mass, pH and O2 levels, potentially very valuable for tissue culture based research programmes.
As well as a fairly intense scientific programme, there were some more relaxed moments. One of great significance was a "special" session where the organisers surprised Professor James Kirkpatrick with a series of talks dedicated to his career in bone and tissue engineering, timed to mark his official retirement from Mainz.  James has a long association with Sheffield through the EXPERTISSUES network where he was a frequent and memorable speaker on our courses, and also as an external examiner.  He is undoubtedly one of the most important figures in the global regenerative medicine community, and it was wonderful to be able to be part of a relatively small group to show our appreciation for his enormous contribution.  James assured me he would remain very active even after retirement!  The meeting ended on Saturday where Simon Pool and I were able to use the local wifi to watch the Wales v Australia before a very enjoyable conference dinner in a traditional restaurant. Katja Schenke-Layland had put together a very impressive scientific meeting where I think everybody left with good ideas for future research and new collaborations, the next meeting will be in Munich and it will be an essential destination for all of us.
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Innovations in Healthcare Conference 2015!

Monday 13th July sees Sheffield's Innovations in Healthcare Conference open a week long series of events that demonstrate the importance of health technologies and medical devices in Sheffield and the local region.  Innovations in Healthcare is again themed very much on making the University's significant research expertise and capacity even more accessible to the medical devices and related health technologies industry.  We have also extended this theme to include consideration of careers and employment, a natural extension from research collaboration.  These are all important subjects, related of course to the region's and indeed the UK's ability to innovate and remain at the forefront of a significant global industry.  However, the speaker I am most excited about will not be talking about the University or even our industrial partnerships, but she will instead tell us something of her life has been enhanced by healthcare technologies (as well as I'm sure sharing some of the limitations of what we in the academic community consider to be state-of-the-art!).
Claire Lomas is becoming increasingly well known as an adventurer who pushes the boundaries of what is meant to be achievable after a serious spinal injury.  Claire lost the use of her legs after a riding accident in 2007, yet in 2012 she donned a robotic exoskeleton and walked full London Marathon...in 17 days.  I like many tuned in to watch her cross the finish line, a moving and inspirational moment that coincidentally brought medical robotics into the public eye.  My recollection is that the London Marathon organisers refused to award her a medal for being too slow, although I note that most online sources say little about this and instead focus on the large number of runners who sent her their own medals in recognition of her accomplishment.  In the context of our Innovations in Healthcare Conference, Claire is significant because she reminds our community that research and its translation into real products and devices is intended primarily to help real people live full, pain free, and - sometimes - very exciting lives.  While doing this at the same time our research base and competitive manufacturing industry create and sustain many thousands of jobs, employment that reaches into an incredibly diverse supply chain and ultimately into UK society.  The diversity of our supply chains should not be underestimated, ranging from raw materials to quality assurance, intellectual property law, regulatory affairs, and of course clinical placement and use by real patients. Innovations in Healthcare will open a very full week that will see every aspect of medical devices and healthcare technologies covered.  Do check our many websites and news items, it might not be too late to make a last minute visit and be inspired!

https://www.eventbrite.co.uk/e/innovations-in-healthcare-conference-2015-tickets-16081967598

http://www.eventbrite.com/e/visible-difference-an-interdisciplinary-symposium-tickets-17095841121

Final thoughts on REF2014 and UK Dental Schools

There has been relatively little critical analysis of the data from REF2014 compared to previous exercises.  While the reasons for this lack of interest remain unclear, it may be in part because individual Units of Assessment (UoAs) were so large as to make subject or institutional comparisons relatively meaningless.  The situation was made more complex by the different strategies adopted by institutions (and indeed different strategies developed by individual teams within institutions).  There have been very few criticisms of the large and often unusual combinations of subjects in different UoAs, either from the individual institutions, the wider academic community, or the media. It could therefore be assumed that the situation is generally approved or at least tolerated.  Inevitably though different research groups seek to compare their performance against peers, especially where critical analysis provides insight into best practice in terms of quality or impact.  The aim of this brief review is to determine how different institutions with Dental Schools performed in REF2014, and consider whether a more detailed and useful analysis could be performed on the basis of the data available.

The UK has 18 institutions with a Dental School or similar academic unit delivering dental education (see Table 1). Not all of these institutions made a return to UoA3, and even where they did it was not always possible to be certain that the institutional return included any staff active in dental research.  What is clear though is that the University of Liverpool, the University of Edinburgh, and the University of Aberdeen did not appear in the list of institutions that returned to UoA3, so in the event that dental and related research was submitted it would have been to a different UoA.  The remaining 15 institutions were listed in the UoA3 documentation available on the HEFCE website (http://www.ref.ac.uk/). 

Table 1:  UK academic institutions with a Dental School or related departmental activity alongside data from REF2014 for UoA3.  Note that this is the total number of staff submitted to UoA3 for each institution, the specific number of Dental School staff submitted to REF2014 is not known.

The summary data for UoA3 shows that 83 institutions made 94 submissions in total (as a number of institutions made multiple or joint submissions).  While this situation makes comparison more challenging, of the universities listed in Table 1 only four made multiple returns to UoA3 (Queens Belfast, Kings College London, Sheffield, and University College London).   The results of REF2014 were analysed by a number of independent parties including the Times Higher Education Supplement (THES), Research Fortnight, The Guardian, and a number of professional blogging sites such as Wonkhe (who utilised additional data made available by Exeter Consulting Ltd.).  Further data on staffing levels was made available after the release of the REF results by HESA, and this shed more light on differences between institutions. While few sources agreed on their detailed analyses, there appears to a be general consensus that (1) the data generated was probably less meaningful than REF2008, (2) the main winners of the exercise were the “golden triangle” institutions (especially large universities in London), and (3) of course the majority of individual institutions were able to generate “good news” headlines for their websites and press releases.  

Research Professional usefully combined the separate submissions made by individual institutions to UoA3 to produce a simplified institutional ranking i.e. each institution only appeared once in its league tables. This data was available on their secure website for subscribers at the time of writing, see (https://www.researchprofessional.com/media/pdf/UoA03_Allied_Health.pdf).  They weighted the data to create a number of useful metrics including Quality Index (a weighting based on the funding allocation, where 4* research is awarded 75% and 3* 25%), Power (how the Quality Index compares to the top performing University in terms of numbers of staff submitted) and Market Share (an estimate of the proportion of actual funding the institution will receive based on REF performance).  This data can be applied to produce league tables for institutions returned to UoA3 where it might be reasonably assumed that dental school staff contributed to the data.  Ranked by number of staff submitted to UoA3, Sheffield was one of the major contributors.  Again it is impossible to know how many dental staff were part of the overall figures (and even where a UoA3 return was named “dentistry”, this was misleading as it typically included staff from other health professions such as nursing or communication science).  By combining knowledge of the affiliation of UK Dental School with this combined REF data, it is possible to produce the institutional rankings given in Figure 1 below.

It may be argued that REF2014 was relatively unhelpful if one wanted to determine differences between specific subjects or departments as well as institutions (and therefore this was most likely the intention of those who were most closely involved in planning and execution).  Extending this argument, the only real beneficiaries were the “golden triangle” including the large London institutions, and it might also be concluded that they in some way disproportionately influenced the planning with this objective in mind.  It is therefore surprising how little public criticism there has been of REF2014 to date, with the few critical comments appearing to focus on the usual arguments i.e. how wasteful (in terms of time and resources) the whole exercise is, and how unhelpful the REF is as a tool to inspire and motivate academics to produce great research and scholarship.  That said, while my personal view is that there has been relatively little in depth or critical analysis of REF2014 compared to previous exercises, it should be acknowledged that a number of very good articles and blogs do stand out.  For example, the Times Higher Education Supplement has reflected some of the wider frustrations in the academic community, and John O’Leary produced a very insightful blog for Wonkhe (http://www.wonkhe.com/blogs/rankings-data-tables-and-spin/).  It would be wise for academics to promote ongoing discussion towards a fairer and more insightful analysis if this activity is going to be repeated in 2020, if the community remains silent we will undoubtedly see something that closely resembles the unremarkable REF2014.

With respect to the relative position of UK Dental Schools, at first sight it may appear impossible to compare performances using the results of REF2014.   Relatively few of the institutions returned in UoA had a dental school, some institutions chose not to return to this UoA, and others split their return across two or three submissions. Even where a split return was termed “dentistry”, an unknown proportion of the actual staff and subjects concerned would have been drawn from outside of the dental schools.  That said, almost all institutions and indeed dental schools have found some pieces of processed data to include on their web sites to demonstrate success in REF2014, but it is widely acknowledged this is related far more to marketing than any meaningful measure of difference.  Rankings of UoA3 based on power rating, then corrected for proportion of eligible staff returned, would provide useful comparisons but currently this is not possible (and it is unlikely to become possible in the future).  If it is essential that Dental Schools are compared, then this can only realistically be performed at the level of combined entries to UoA3 under power rating.  Sheffield lies 3^rd among institutions with a Dental School on the basis of both quality and power, in many ways a very satisfactory result. Ultimately though it is the financial benefits of a strong REF performance that matters most, and any artificial ranking will be less relevant in the absence of a cash reward.  The information that has emerged thus far suggests that this REF and subsequent adjustment of the national funding formula has been an exercise to further concentrate investment in London, Oxford and Cambridge at the expense of the N8, and northern Dental Schools could therefore suffer the ill effects of a badly executed REF for several years to come.  There now needs to be some response from the academic community who understand the value of an exercise performed well, and this includes the majority of UK Dental Schools who wish to maintain their important, distinctive and clinically relevant research for the benefit of the UK, including our industry and ultimately our patients.

Additional notes and data:  Research Professional also ranked institutional submissions to UoA3 by their Quality Index (Figure 2).  Differences in Quality Index were not as great as those seen in Figure 1 (above), with the greater discrimination by Power in part due to the number of institutional staff returned to this unit of assessment.  The different institutional policies are apparent here, for example KCL made a large return and benefitted in the Power Rating ranking (Figure 1), whereas Cardiff made a smaller return with a greater focus on quality, therefore coming 2nd in the Quality Index but falling to 5th in Power (it has been argued that as Cardiff are separately funded to the other UK institutions they were more interested in external perceptions of quality rather than the final HEFCE financial calculation).

What to say at Sheffield University's Industry Day?

On 6th March, I will have* the privilege of welcoming over 300 business delegates from across the whole medical devices and health technologies supply chain to the University of Sheffield.  Specifically, I have 15 minutes to introduce the day and explain why every year we set aside one day for this key sector.  This is of course not a difficult task in the sense that the drivers for innovation are well known, and they connect all of us whether we work at the laboratory bench, in a law firm specialising in patents, in a manufacturing industry in production or marketing, or indeed in a hospital.  These drivers include the ageing population, increased patient expectation, new scientific discoveries, regulatory pressure, free market competition, clinical advances, and wider government policies.  It is relatively easy for a professor in the field to construct a stimulating welcome speech based on this sort of material, coupled to examples of academic-industrial collaboration benefiting both parties, and ending with an enthusiastic invitation to delegates to talk to the University about their company's research needs to discover what we can do to help.  It might be that this is exactly the talk I will give, hopefully offering insights that will be new to at least some of the audience, but nevertheless a relatively safe presentation.

I have, however, just opened a picture taken last year of my elderly grandmother sitting next to my eight year old daughter, and I feel that this image is challenging me to raise some deeper challenges as a part of my welcome speech.  The image of my daughter reminds me that our generation have a special responsibility to create prosperity and jobs in the future, and high value manufacturing as found in the medical devices and health technology sector is exactly the kind of industry that can perform this service for the UK and Europe.  I have come to believe that responsible job creation is one of the most important things people in senior positions do - or should seek to do - whether in industry, or in universities, or within other parts of the supply chain.  Younger people have suffered disproportionally in this recession, and as we emerge it is important we create opportunities for them to flourish. I was fortunate to open a small meeting where a number of new health technology companies that had been started by young graduates presented on their work and business growth.  They were still small companies, but in only a few years had grown from one or two people to half a dozen.  What really struck me though was the energy, optimism and determination of these young entrepreneurs, and I was left with a reminder of what young people can achieve if they are given opportunities.  The task for those with power and influence is to provide those opportunities.

My gran is of course at the other end of the age spectrum, and she is now suffering from several of the problems that we associate with old age including dementia and failed hip replacements.  These past few months have seen her moved from care home to city hospital and then on to a small hospital, she is almost certainly at a point in life where she is unlikely to "get better" and the best she can hope for is to be made as safe and comfortable as possible.  Many people have experienced, or will inevitably experience, parents and grandparents ageing to the point where they are robbed of good life quality.  Seeing my gran, I feel strongly that she was previously denied interventions that could have prolonged the life of her infected hip replacement.  She was not denied these on account of her age or NICE guidelines or clinical incompetence, she was actually denied a potentially efficacious intervention by the regulatory environment.  As a result of my research I know that there are very many technologies that could be employed to eliminate or reduce the severity of a device associated infection, but the regulatory burden associated with drug-device combinations or silver-containing products is so high that it is simply not economic for companies to invest in taking these products to market.  I have though formed the view that the elderly need access to more potent health technologies than other patient groups, and even if the associated risks are greater I think this is a risk worth taking.  My gran's life expectancy is shorter than mine, she is not going to have children, her risk of cancer is low, and her innate capacity for self-repair is non-existent - by definition the types of medical device and health technology she needs are different to a younger patient, and the risks are different too.  Yet the current regulatory environment does not even try to discriminate between the needs of different patient groups, or indeed the different risks they face.  I think these are the types of questions that academic groups should have the courage to ask, and the whole health technology community should invest resources in making a more detailed argument to government and regulators.  I feel that my gran and thousands of elderly patients deserve interventions that will give them not only a long life but a good life.  More selfishly, when I am old I want the clinicians treating me to have access to products that meet my specific needs, ideally products born from UK intellectual property and made by our manufacturing industry.

I do not know yet though if I will tackle this more complex and controversial subject in my opening, ask me in the comments section below.





*Or by the time most of you read this, "will have had".

PIP Breast Implants: Who is responsible?

The manufacture of breast implants using a non-medical grade silicone is a saga that runs on and on, not only for the victims who received PIP devices but also for the companies in the supply chain, the surgeons, the regulators and (of course) the lawyers who are arguably the only beneficiaries of this disaster.  Today a French court appears to have determined that a German "Notified Body" (a legal entity who is considered competent to recommend whether or not a CE mark should be awarded) shares some of the blame for this disaster.  You will need to note here that a CE mark is necessary to place a medical device on the open market in Europe.  It is not a "safety certificate", it is simply a mark of compliance with European law (albeit European law that was implemented as a risk reduction measure).

For the lay person, this is a very confusing subject, and the BBC have tried hard but probably failed to make this story easier to follow (see: BBC story on the recent legal case.).  Why is this story so confusing, and why then is it so difficult to determine precisely who is to blame?  To answer these questions, you have to find the answers to a number of other related questions that are being scrutinised by lawyers and regulators throughout Europe.  These include (1) Was the PIP breast impact actually a medical device or instead a mad-made component to be used in a purely cosmetic and non-medical procedure, (2) Were the regulators to blame for not having strong enough definitions to answer question 1, (3) Was the "Notified Body" to blame for incorrectly recommending the award of a CE mark on the basis of their inspection (if indeed this is what they did, and as an appeal has been launched we need to be careful not to assume), and even (4) Were the private clinics, hospitals and surgeons to blame for not wondering why these French implants were cheaper than the majority of devices on the market.  These are all important questions, but given the legal result reported today, I want to comment mainly on number (3), was the "Notified Body" TUV Rheinland really responsible?

As a Notified Body, this company had the job of checking the documentation regarding design and specification for a medical device, as well as the quality of the manufacturing environment (including quality assurance processes).  The nearest analogy that a lay person might understand - at least in the UK - is the garage that checks the safety of your car before awarding an MOT certificate.  If you were to use low quality brake components - perhaps purchased off eBay - that did not work properly, you would expect a diligent mechanic to detect this and your vehicle would fail the MOT.  If the mechanic did not test the breaks, and you were awarded an MOT shortly before killing a pedestrian because you failed to stop at a crossing, it could be construed that the mechanic and his/her employer were in some way responsible.  My view though is that the vehicle owner who fitted the "dodgy" components is really responsible, and all the more so if they deliberately fitted the parts knowing they were sub-standard. 

In the case of the PIP breast implants though, I expect that TUV Rheinland will claim that the French manufacturer deliberately lied in their documentation and hid the malpractice from them.  In this case, it is as if you re-fitted high quality brake components for the purposes of passing your MOT, but then took them off immediately after obtaining your certificate.  It would be very unfair to hold the garage responsible if you then caused an accident, but this appears to be the decision of the French court. Of course this comes to whether or not the German Notified Body did its job properly, and also what the law says about responsibility in this case.  Perhaps at appeal we will find out.

The only other comment worth making is on my first question, are PIP breast implants medical devices?  This is very important, because in this context only medical devices need CE marks.  The fact that the manufacturer applied for a CE mark suggested that - at least in some cases - they expected the device to be used in a medical procedure (for example, in a breast reconstruction following mastectomy).  However, if the device was for purely cosmetic enhancement of breast shape and size, this was arguably a purely cosmetic procedure and it is probably the case that the medical devices directives would not apply.  Now the average person might think the same quality and manufacturing standards should apply, but the fact is that they do not (at least not in any legal sense), and a short visit to eBay shows that people may be surprisingly relaxed when it comes to the purchase of so-called cosmetic materials such as powerful tooth bleaches from Hong Kong, "Botox effect gels", and home made cosmetics, none of which come with any safety or quality checks.  If the manufacturer used medical grade silicone for the implants to be used in medical procedures, and a lower grade filler only for cosmetic implants, then he may yet deflect the full force of justice.

I have written another article on this subject that questions the role of the purchaser in this debacle (usually a private clinic, but also NHS hospitals), and even ponders whether or not clinicians should today take a keener interest in the provenance of the medical devices that they use?  All of these questions and more are difficult to answer, the only certainty for now being that lawyers will be reaping the benefits of this uncertainty for many years to come.


 

Ethics Abandoned: What do shameful practices among some military medical personnel have to do with innovation?

This week saw the release of a long-awaited report on doctors in the US military, and it concluded that some had been complicit in the torture of detained suspects.  This report makes interesting and at times depressing reading, but it should be noted that these are a tiny tiny minority of healthcare professionals, and this is certainly not an indictment of modern medicine as a whole.  You can read more here, with a link to the report itself at the bottom of the post: http://www.theguardian.com/world/2013/nov/04/cia-doctors-torture-suspected-terrorists-9-11

While this failure to adhere to ethical codes and professional standards was probably a greater problem in the USA, the UK profession has not been immune (the best example being Derek Keilloh, struck off for his complicity in seeking to cover up the fatal injuries of Baha Mousa received while detained by the British Army).  There is much written on these emotive subjects, and those who are interested can find plenty to digest and debate elsewhere.  This did, however, make me think more broadly.  The interesting questions here then are do professional standards and ethical codes for doctors and dentists matter in the world of health technology innovation, and if they can be eroded in a military setting could they also be undermined when working with businesses or even universities? 

In my dealings with healthcare professionals, I am always impressed by the strong emphasis of what is in the best interests of the patient above all other considerations.  This strong moral foundation is not new, it can be traced back to (among others) Hippocrates and the oath that is still taken by many physicians today (including in the UK and USA).  Clinicians and their professional bodies take a dim view of colleagues who fall short of these high standards, and thankfully the available evidence shows that very few doctors do transgress.  That said, this tiny minority includes a number of clinicians who were perhaps overly influenced by commercial factors, or who at least paid insufficient attention to the of the medical devices they were using.  One example was the use of poor quality PIP breast implants by countless surgeons, where the major determinant of implant selection appeared to have been (low) price.  This may not be a fair example, it is unlikely that the surgeons themselves were involved in procurement, but I have argued in a previous article (The PIP breast implant scandal: lessons for dental implantology Faculty Dental Journal volume 3 pages 68 to 72) that perhaps surgeons should concern themselves more with the quality of medical devices being purchased by their hospitals, and if purchasing decisions are made solely on the basis of the lowest price then quality will fall and ultimately patients will suffer (if you disagree, just think about the contents of Tesco's value lasagne).  Of course this is not wilful disregard for professional standards or even dishonesty, and where new health technology innovations go wrong it is very unlikely that deliberate clinical malpractice is to blame.  What the behaviour of a few US military doctors, Derek Keilloh, and some surgeons associated with the PIP scandal, tells us is that working environment and prevailing culture can have a subtle but sometimes very negative impact on personal and professional ethics.  Society would be wise to consider this risk when we place medical professionals in places where their training may not have prepared them fully for the new environment.

If this subject attracts some interest and comments, then I would be happy to follow up with some more detailed analysis of medical device disasters, ancient and modern, and we can look at the roles of the professional and the industry.  For now though, I remain very confident that the vast majority of clinicians engaged in the development and evaluation of new healthcare technologies do so because that are motivated by the highest values of the caring professions, and therefore what is in the best interest of the patient.

Link to the IMAP report: http://www.imapny.org/medicine_as_a_profession/interrogationtorture-and-dual-loyalty